Technical Briefing from the CDC
Let’s examine the last technical briefing from the CDC (Ref. 2) before these latest developments. It was updated on December 29, 2023. It reported, “A small number of sporadic human cases of A(H5N1) have been identified since 2022, despite the panzootic of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in wild birds and poultry.” Let me interpret that for you. First, “A(H5N1)” is an abbreviation for A (influenza A)
H5 (hemagluttinin subtype 5) [explanation – influenza virus has an envelope (not all viruses do). Hemagluttinin is the major protein found within the envelope. It is both involved as a site for binding to cells to cause infection, but also a target for neutralizing antibodies. There are 18 antigenically distinct (meaning that our immune responses to one form of hemagluttinin may provide little, if any, cross-reactive protection against another) subtypes of hemagluttinin protein – (H1 – H18).
N1 (neuramidinase type 1) [explanation – neuramidinase is another envelope protein that plays a number of roles in the transmissibility of the virus, the infectivity of the virus and in the release of viral progeny once reproduced in an infected cell. There are 11 antigenically distinct subtypes of neuramidinase protein – (N1 – N11).
The CDC is pointing out some reassuring news that despite the wide spread transmission of A(H5N1) in wild birds and poultry (panzootic is the equivalent of a pandemic, but limited predominantly to non-human animals), there have been only limited numbers of cases of infections recognized in humans, and these have been sporadic (e.g., not causing outbreaks of human-to-human spread).
The CDC goes on to state, “Nearly all reported human cases since 2022 were associated with poultry exposures, and no cases of mammal-to-human or human-to-human transmission of HPAI A(H5N1) virus have been identified.” In other words, they could tie almost every case in a human back to an exposure to poultry rather than cases with no known exposure that would significantly raise the suspicion for human-to-human transmission and community spread. This would imply that the A(H5N1) virus seems poorly adapted to infect humans and transmit forward from humans. However, the CDC goes on to state, “In a few cases, the source of exposure to HPAI A(H5N1) virus was unknown.” This is the qualifier that implies, while it overwhelmingly appears that human cases of A(H5N1) are related to zoonotic spread from animals to humans, we can’t be sure that there is no human-to-human transmission, though even if there is, that transmission is not efficient (doesn’t happen easily, widely and sustainably).
Why aren’t more humans getting infected from animals and transmitting it on to their close contacts? “To date, HPAI A(H5N1) viruses currently circulating in birds and poultry, with spillover to mammals, and those that have caused human infections do not have the ability to easily bind to receptors that predominate in the human upper respiratory tract.” One of the major factors of virus fitness for human infections is its ability to bind to receptors present on our cells that would in turn allow the virus to enter and infect the cell, and then hijack the cellular machinery in order to prioritize making new copies of the virus over proteins for the cell’s own needs. In this case, this virus doesn’t seem to be able to bind human cell receptors very well to promote infectiousness of humans.
The CDC ends their briefing making the assessment that the public health risk from A(H5N1) is low. As of 3 months ago when the CDC made this assessment, I would have agreed with that judgment. I still believe that the risk is low at this point, but we do have to acknowledge that the ever expanding list of mammals that the virus is able to infect, the greater the chance that the virus can develop the capability to improve transmission to and among humans. Further, the infection of cattle raises the potential of threat to our food chain, though that threat has not materialized as of yet. In addition, given the breadth of new mammal hosts and the infection of cattle on farms, we must have heightened concern for the potential of the virus to infect pigs with a resultant reassortment of the virus genes such that transmissibility to humans is increased.
Monitoring of animals in the U.S. for HPAI A(H5N1)
The U.S. Department of Agriculture’s Animal and Plant Health Inspection Service (APHIS) monitors for avian influenza viruses in the wild, commercial and backyard birds. For 2022 and 2023, APHIS reported HPAI A(H5N1) virus detections in more than 8,500 wild birds in 50 states and territories and more than 1,000 commercial and backyard flocks affecting 77.9 million birds in 47 states.
APHIS also made 207 detections in mammals comprising 21 species in 27 states. Here is the map as of the end of 2023:
What was the recent development?
The first case of A(H5N1) infection in U.S. livestock was a goat in Minnesota discovered earlier this month. A(H5N1) monitoring turned up cases of the virus infecting U.S. dairy cows, the first time the virus has ever been detected in cattle. Texas, Kansas and New Mexico reported sickened cows on March 25, 2024. Dead birds had been discovered on some of the farms, which may explain the source of the virus infection. As of the time of this writing, the virus has only been confirmed by genetic testing in the Texas and Kansas cattle, and it was reported that the genetic sequence was that of the virus found circulating in birds. Even more recently, cows tested positive in Idaho and Michigan. The spread of symptoms among some of the Michigan cows has raised concern for whether there could be transmission among cattle. Further, it has been reported that some of the Michigan and Idaho cows were obtained from Texas.
Even when avian flu infects animals, we have detected little evidence for ongoing transmission, but rather it has been assumed that most of the animals had exposure to birds. However, the simultaneous onset among several states, including cases in which cattle originated from one of the other states has raised the question as to whether there is now forward transmission of infection among cattle. We may be able to determine that by sequencing samples among different herds in different states, however, in the meantime, the National Veterinary Services Laboratories indicated that they had not seen any changes in the current samples in comparison to past samples that would suggest to them that the virus has fundamentally changed.
While it does not appear to me from what I can see in public reporting that cattle are dying in the ways that we have seen with migratory birds and seals, for example, there are reports that the cattle have become sick manifested by decreased appetite, weight loss and decreased milk production. The USDA has indicated that cow milk is safe to drink as long as it is pasteurized.
So why is this a big deal?
I don’t know whether it is a big deal, but it is concerning that the range of hosts that this virus is infecting has broadened to include hosts that we don’t see avian influenza in – e.g., carnivores like bears, wolves and foxes and now livestock like goats and cows. That suggests that something has changed – the virus, the hosts, the environment, etc., it just remains unclear as to how to explain this at this time. The evidence has supported that the transmission of avian influenza among birds has been fecal-oral. The concern that needs to be tested is whether there could be airborne transmission. Further, when we see increased transmission and especially if there is transmission within species, we will see more mutations and reassortments that certainly increase the risk that the virus could adapt to transmit more efficiently to humans.
My big fear? I know next to nothing about farming being a city boy, but I did go to visit my grandpa on his farm when I was a kid. Guess what I saw on the farm in addition to the cows? Pigs. (If that doesn’t give you an aha moment, you need to reread the first part of this blog piece again).
Even if this virus continues not to pose a significant threat to humans, I do think we have to worry about the ecological changes of so many animal species being affected and dying off. If this is going to be an increasing issue for transmission among livestock, we also have to worry about the impacts to the food supply. We have already seen the rise in prices for eggs due to the need for chickens to be culled in cases where A(H5N1) was found. It would be unlikely we would do the same with cattle, but the question is whether as we see more infections in cattle, do we see loss from the infection itself.
I think it is way too early to tell, but some early reports suggests that the cows were getting more of a gastrointestinal illness rather than the respiratory illness generally seen in other animal species. If that bears out over time, is that because of a change in the virus (e.g., receptor targets) or is it something unique to cattle?
What do the real experts have to say about this development?
The USDA, FDA and CDC issued a joint press release on Friday, March 29 (See reference 6). They informed the public that in addition to confirmation of HPAI in two dairy herds in Texas, they had since confirmed HPAI in two dairy herds in Kansas. The USDA’s National Veterinary Services Laboratory also confirmed HPAI in the Michigan herd that had received cows from Texas. They also reported presumptive, but not yet confirmed tests of cows for HPAI in Idaho, New Mexico and Texas. The agencies reported that the strain of HPAI appears to be that circulating in wild birds, and they indicated that mutations that would be concerning for human transmission have not yet been detected. Their risk assessment was that human infection is believed possible with direct contact with infected cattle, but the risk to the general public remains low.
Recommendations at this point have included:
- Continue to monitor.
- Separate sick cattle from those that appear well.
- Minimize movements of cattle.
- Milk from sick animals continues to be diverted or destroyed and will not enter the commercial market. The agencies express no concerns about the safety of the commercial milk supply because all commercial milk is required to be pasteurized.
The CDC also has indicated its plans and I think they are very good:
- CDC is actively working on the domestic situation with clade 2.3.4.4b HPAI A(H5N1) viruses in wild birds and poultry outbreaks, including conducting surveillance among people with relevant exposures and preparing for the possibility that contemporary HPAI A(H5N1) viruses gain the ability for increased transmissibility to people.
- CDC, along with our state and local public health partners, continues to actively monitor people in the United States who have been exposed to infected birds and poultry for 10 days after exposure. To date, more than 7,000 people in 52 jurisdictions have been monitored since 2022, and only one human case has been identified.
- H5 candidate vaccine viruses (CVV) produced by CDC are expected to provide good protection against current clade 2.3.4.4b HPAI A(H5N1) viruses in birds and mammals. These H5 CVVs are available and have been shared with vaccine manufacturers.
- Because influenza viruses are constantly changing, CDC performs ongoing analyses of HPAI A(H5N1) viruses to identify changes that might allow for spread more easily to and between people, cause serious illness in people, reduce susceptibility to antivirals, affect the sensitivity of diagnostic assays, or reduce neutralization of the virus by vaccine induced antibodies. To date, few changes in HPAI A(H5N1) viruses of public health concern have been identified and such changes have differed between various HPAI A(H5N1) viruses circulating in wild birds and poultry worldwide or that have sporadically infected humans.
- Currently, HPAI A(H5N1) viruses circulating in birds are believed to pose a low risk to the general public in the United States; however, people who have job-related or recreational exposures to infected birds may be at higher risk of infection and should take appropriate precautions outlined in CDC guidance.
- Comprehensive surveillance and readiness efforts are ongoing, and CDC continually takes preparedness measures to be ready in case the risk to people from HPAI A(H5N1) or other novel influenza A viruses changes.
In addition, the CDC issued a report entitled: “Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations” on Friday (Reference 7). The key points of this guidance are as follows:
- Most human infections with A(H5N1) have occurred after unprotected exposures to sick or dead infected poultry.
- There is no evidence of sustained human-to-human transmission, and limited, non-sustained human-to-human transmission has not been reported since 2007.
- Influenza A viruses infect both the respiratory and gastrointestinal tracts of birds causing the infected birds to shed virus in their saliva, mucous and feces.
- Human infections can result from getting enough of the virus in the eyes, nose, mouth or inhaled into the lungs.
- Illness in humans can range from mild (upper respiratory tract symptoms) to severe (pneumonia, multi-organ failure) illness resulting in death.
- People should avoid unprotected exposures to sick or dead animals, as well as animal feces, litter and materials contaminated by birds or other animals with suspected or confirmed HPAI A(H5N1) virus infection.
- Avoid preparing or eating uncooked or undercooked food, such as unpasteurized (raw) milk or raw cheeses from animals with suspected or confirmed HPAI A(H5N1) infection.
- Personal protective equipment (PPE) should be worn when in direct or close contact with sick or dead animals, their feces, litter or other contaminated materials. This includes properly fitted unvented or indirectly vented safety goggles, disposable gloves, boots or boot covers, a NIOSH-Approved particulate respirator, (e.g., N95 filtering facepiece respirator, ideally fit-tested), disposable fluid-resistant coveralls, and disposable head cover or hair cover.
- People exposed to HPAI A(H5N1) virus infected birds or other animals should monitor themselves for new respiratory illness symptoms, including conjunctivitis (eye redness) for 10 days after their last exposure, even if they were wearing appropriate PPE. Antiviral post-exposure prophylaxis can be considered. Persons who develop any illness symptoms should seek prompt medical evaluation and should isolate away from others, including household members, until it is determined that they do not have HPAI A(H5N1) infection.
References:
- Textbook of Influenza, 2nd ed., Webster, RG; Monto, A.S.; Braciale, T.J.; and Lamb, R.A. Wiley Blackwell 2013.
- CDC technical briefing https://www.cdc.gov/flu/avianflu/spotlights/2022-2023/h5n1-technical-report_december.htm. Updated December 23, 2023.
- Structural Biology of Influenza Hemagluttinin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551194/.
- Bird flu discovered in U.S. dairy cows is “disturbing.” https://www.science.org/content/article/bird-flu-discovered-u-s-dairy-cows-disturbing
- The changing dynamics of highly pathogenic avian influenza H5N1: Next steps for management & science in North America. https://doi.org/10.1016/j.biocon.2023.110041
- https://www.aphis.usda.gov/news/agency-announcements/usda-fda-cdc-share-update-hpai-detections-dairy-cattle
https://www.cdc.gov/flu/avianflu/hpai/hpai-interim-recommendations.html
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