From Poultry to Public Health: Understanding the H5N1 Threat

Unpacking the current threat landscape

Avian influenza (HPAI) A(H5N1), commonly known as bird flu, has had an increase in human cases in the United States recently, particularly among poultry and dairy workers. H5N1 has primarily circulated in the Midwest, with these cases raising concerns about potential human transmission and broader public health implications. Understanding the current landscape of H5N1, including recent data and prevention strategies, is essential as health officials monitor the situation.

The CDC is monitoring influenza data at national, state, and local levels. As of October 9, 2024, 18 human cases of H5N1 have been reported in the US since 2022. Since February 2022, more than 15,500 individuals have been monitored after exposure to infected animals, with 590 tested for novel influenza A. Recently, approximately 6100 individuals have been monitored, including 3350 exposed to dairy cows and 2800 to birds and other animals.1

Currently, CDC surveillance systems indicate no unusual flu activity related to H5N1. In the week ending October 19, 2024, public health laboratories reported no positive tests for novel influenza A, and wastewater monitoring detected H5 at only 1 out of 320 sites.1

CDC continues to collaborate with the USDA, FDA, and state health officials using the One Health approach to monitor the situation. The agency has deployed a multilingual epidemiological field team to assist local health departments with outreach and surveillance efforts. To date, more than 5100 individuals exposed to potentially infected animals have been monitored, and more than 54,000 specimens have been tested for H5N1viruses.2

Stay safe: Essential tips for protecting yourself from H5N1

A CDC spokesperson shared with Contagion, “The best way to prevent H5N1 bird flu is to avoid sources of exposure whenever possible. Recommended precautions include:

• Avoid direct contact with wild birds and observe them only from a distance, if possible.
• Avoid contact with wild or domestic birds that appear ill or have died. People should report sick birds or other animals or unusual bird or other animal deaths to the state or the federal government, either through their state veterinarian or by calling USDA’s toll-free number at 1-866-536-7593.
• Avoid unprotected direct physical contact or close exposure with cattle and materials potentially infected or confirmed to be infected with HPAI A(H5N1) virus.
• Do not touch surfaces or materials contaminated with saliva, mucous, or animal feces from wild or domestic birds or other animals with confirmed or suspected avian bird influenza A virus infection.
• Do not eat or drink raw milk or products made with raw milk.
• If you must have direct/close contact with infected or potentially infected birds or other animals, wear recommended personal protective equipment (PPE).”

Spotlight on Recent Cases

A notable case in Missouri marked the 14th reported case this year and was the first without documented occupational exposure. Identified through seasonal flu surveillance, the patient was hospitalized but has since recovered. Experts suggest that transmission routes may include incidental contact with infected animals, indicating a need for further research into risk factors.3

Megan Davis, DVM, PhD, MPH, an associate professor at Johns Hopkins Bloomberg School of Public Health, discussed potential alternative transmission routes for avian influenza, highlighting the Missouri case as an example of variable exposure routes beyond direct animal contact. “What the case in Missouri really highlights is that the transmission routes are quite variable. It’s not just occupational contact with live animals; it could also be from incidental contact with animals, and we don’t yet fully recognize what those risk factors might be for people,” she said.

The serological testing methods used in the CDC’s investigation of the Missouri H5N1 case included several assays. The primary method was the Microneutralization (MN) assay, which identifies influenza virus-specific antibodies in blood sera by measuring the ability of these antibodies to neutralize the virus. The Hemagglutinin Inhibition (HI) assay was employed to detect antibodies to the hemagglutinin of specific influenza viruses; this test assesses the ability of antibodies to agglutinate red blood cells, using multiple types of red blood cells for detection.4

Another method used was the Multiplex Antibody Detection Assay (MIADA), which looks for antibody binding to multiple influenza antigen targets (28-plex) and measures total immunoglobulin responses, including IgG, IgM, and IgA. A Seasonal Influenza Serum Absorption step was included to remove antibodies against seasonal influenza viruses to reduce cross-reactivity, enhancing the specificity of the H5N1 testing.4

The CDC also developed 2 Reverse Genetics (RG) viruses that mirrored the antigenic changes found in the H5N1 virus from the Missouri case. This allowed for precise serological testing. Together, these methods provided a comprehensive assessment of immune responses and potential previous exposure or infection with H5N1 in the individuals tested.4

More recently, in California, the Department of Public Health confirmed 7 probable cases of H5N1 linked to dairy farm outbreaks. Most infections have occurred among farm workers, with mild symptoms reported.4

To continue, the CDC confirmed H5 infections in two of four poultry cullers from Washington state, marking the state’s first cases. Despite the confirmed cases, public health officials maintain that the risk to the public remains low, although those with occupational exposure to sick animals face a higher risk.5

Despite the rise in cases, Davis said, “The good news, however, is that despite the human cases linked to poultry outbreaks and dairy cow infections primarily affecting workers, no human-to-human transmission has been identified yet. This is an important aspect to monitor closely.”

One Health: An approach bridging human, animal, and environmental Health

The One Health approach is a collaborative framework that recognizes the interconnectedness of human, animal, and environmental health. It advocates for a multidisciplinary strategy to address health challenges, particularly zoonotic diseases, by integrating expertise from fields like medicine, veterinary science, and environmental science to promote holistic solutions and sustainable ecosystems.

Davis is a proponent of the One Health approach. She said, “One Health is foundational to many infectious diseases that are zoonotic. What is recognized with highly pathogenic avian influenza is that it has been present for a considerable period. Like seasonal influenza in humans, there are influenza strains that predominantly affect birds. These include reservoirs—types of birds that carry the virus but don’t get very sick themselves—such as waterfowl like ducks. On the other hand, there are birds that can become severely ill and die, including domestic poultry like broiler chickens, layer chickens (for meat and eggs), turkeys, and other species kept by humans.”

According to the CDC spokesperson, “CDC’s One Health approach recognizes the interconnection between people, animals, plants, and their shared environment, which is highly relevant in our surveillance and response strategies for H5N1.”

Current status of human vaccine developments for H5N1

According to the CDC’s October 11, 2024, update, the CDC has allocated more than 100,000 doses of seasonal flu vaccine for farm workers in 12 states with positive H5 cases to mitigate the risk of spread. Although the vaccine does not protect against H5N1, the CDC noted that it can reduce severe illness from seasonal flu as well as aid in the identification of potential H5N1 cases.6

Additionally, the CDC is testing existing candidate vaccines for effectiveness against current H5N1 strains. Recent studies suggest that licensed adjuvanted H5N1 vaccines may generate cross-neutralizing antibodies against circulating variants, aiding in pandemic preparedness.1

They are also genetic sequencing of the H5N1 viruses from infected individuals has shown no significant mutations associated with increased infectivity or reduced susceptibility to available antiviral treatments. This is important for understanding the current vaccine landscape, as it suggests that the current vaccines may still be relevant.1

A study published in Nature in July 2024 found the stockpiled adjuvanted H5N1 vaccines demonstrate potential effectiveness against H5N1 clade 2.3.4.4b, highlighting their importance in pandemic preparedness efforts. The study assessed the binding, hemagglutination inhibition, and neutralizing antibody responses in adults vaccinated with three licensed H5N1 vaccines derived from earlier strains (A/Vietnam, clade 1; A/Indonesia, clade 2.1) with and without adjuvants.7

Vaccination with the 2 adjuvanted H5N1 vaccines resulted in cross-reactive binding and cross-neutralizing antibodies against the HPAI clade 2.3.4.4b A/Astrakhan/3212/2020 virus. Seroconversion rates ranged from 60% to 95% after 2 doses of the AS03-adjuvanted A/Indonesia vaccine or 3 doses of the MF59-adjuvanted A/Vietnam vaccine.7

Antiviral options for managing H5N1

Oseltamivir is the primary antiviral, prescribed at 75 mg twice daily for 5 days for outpatients, and should be given promptly to hospitalized patients, regardless of illness onset. For immunocompromised patients, combination therapy may help prevent antiviral resistance. Treatment should not be delayed while awaiting lab results, and duration may be extended for severely ill patients based on clinical judgment.8

Intravenous peramivir is an alternative for those who cannot take oral medications, recommended for at least 5 days. Higher doses of oseltamivir have not shown additional benefits, so healthcare providers should consult CDC resources for dosing guidance. Treatment with antivirals like oseltamivir is recommended for suspected H5N1 cases. Healthcare providers are advised to start treatment without delay, even before laboratory confirmation. Monitoring for antiviral resistance, especially in hospitalized patients, is important.8

Safety measures for veterinary professionals and clients

As avian influenza continues to rise as a threat to animals and the safety of veterinary professionals, it is becoming crucial for teams to understand the disease and how to protect patients, clients, and themselves—especially since avian influenza has now been transmitted to different species, including humans.9 In Spring 2024, Texas reported the detection of the disease in dairy farms and in other animals such as dolphins.

The CDC advises that it is currently unlikely humans can become infected through an infected stray, wild, feral, or domestic cat, but human infection can be possible if there is prolonged unprotected exposure to infected animals in individuals not wearing personal protective equipment.10

“If you have an animal that has a fever, is lethargic, maybe [they are] having some discharge from the eyes or nose, coughing, trouble, breathing, wheezing, and especially an elevated body temperature, any of those flu-like symptoms will be things that you’ll want to be thinking about as potential symptoms of avian influenza,” Kemba Marshall, MPH, DVM, DABVP (Avian), SHRM-CP, founder of Marshall Recruiting Consortium, explained.

“Now, specifically, let’s turn our attention towards backyard poultry. Chickens can do the same things, they can still cough, wheeze, and have discharged from the eyes and nose. Their comb, the skin that you see on the top of their head, you may see that become discolored. Affected laying hens may have an abnormally shaped eggs, which may be kind of lumpy, bumpy, or what we just call like a misshapen egg,” she continued.

Veterinary professionals who suspect that they have a case of avian influenza based on clinical signs, will need to run a polymerase chain reaction (PCR) test. Veterinary teams should wear personal protection equipment (PPE) for all suspect avian influenza cases and while collecting diagnostic samples. For testing, veterinary teams are encouraged to reach out to their state veterinarian prior to sample collection because state labs, which are part of the National Veterinary Diagnostic Laboratory, are often the only labs permitted to perform avian influenza testing. State labs should be contacted before any post-mortem samples are collected to ensure proper sampling techniques. As a reminder, carcass can be refrigerated or chilled but should never be frozen prior to diagnostic sample collection.

Nasal and ocular swabs, urine, and whole blood samples can be submitted to the appropriate diagnostic laboratory. If the suspected animal is deceased, veterinary teams should also submit a 1” x 2” section of brain.10 All samples should be fresh, refrigerated, and shipped in an insulated box with ice packs.

Marshall explained that biosecurity is the key to managing the virus on farms and amongst animals. She encourages anyone coming into your house or farm to wear clean clothing, hats, and shoes to avoid cross contamination and disease spread via fomites. If animals must be transported, it is important to thoroughly disinfect all shipping, handling, and transport areas and vehicles, especially for larger animals on the road for shows or competitions.

“Biosecurity also means we should be able to have a record and a log of every person that came to the fair, animal exhibition, or farm. We want to keep a record of who was there, how long they were there, and if that person had been to other farms that day or that week. Farms should have designated entry points, wheel or vehicle wash stations, and separate holding areas or pens for incoming and outgoing animals. All state ordinances and laws should be followed regarding intra and interstate health certificates” Marshall continued.

“We cannot understate the importance of PPE…. which includes gloves, goggles, gowns, and face masks. In addition, hand hygiene is critical and includes very frequent and thorough hand washing with soap and water. Individuals should be mindful of not handling animals or animal matter and then immediately handling their cell phones. Individuals should not be on their cell phones texting or making notes or anything like that, and then turn around and scroll on that same cell phone when you’re eating your ham sandwich or drinking your coffee,” Marshall noted.

As avian influenza has now been detected in felines, it is recommended to use caution when letting cats go outside, especially if they live within an agricultural setting. The CDC also recommends feline owners who have interacted with animals or birds with unknown health status change their clothes and shoes before interacting with personal pets.11 For owners of potentially infected pets, veterinarians should refer them to their state’s Department of Public Health and Environment in order to monitor human exposure and potential human disease transmission.

For veterinarians, it is recommended to use isolation and appropriate patient handling protocols for suspected infectious and/or zoonotic disease cases, including negative airflow if possible. Staff should contain and thoroughly disinfect any equipment used to treat the potentially infected patient. Staff should wear proper PPE and limit staff contact with animals in isolation facilities to the best of their abilities.

Navigating the risks: How H5N1 might cross into human populations

Wastewater contaminated with the droppings of infected animals may harbor the virus. Individuals who encounter contaminated water or who work in wastewater management could be at risk, especially if proper precautions are not taken.

Genetic testing in wastewater is increasingly used to track the spread of H5N1 in the US, particularly among dairy herds, raising public health concerns. While PCR testing is standard for virus detection, its specificity issues may miss some variants. Recent research found H5N1 in wastewater across nine Texas cities, suggesting animal rather than human sources. Individuals in close contact with infected animals or consuming unpasteurized milk face greater risk. Overall, wastewater testing is becoming essential for disease surveillance.12

If poultry infected with avian influenza contaminates milk products, consuming unpasteurized or raw milk could pose a risk of transmission. Pasteurization typically eliminates such viruses, but raw products carry a higher risk.

Health officials warn against consuming unpasteurized milk due to the H5N1 bird flu virus found in more than 140 US dairy herds and high levels in raw milk. The virus can remain infectious on milking equipment for several hours and in unpasteurized milk for at least 1 hour. The milking process, which involves automated equipment and manual cleaning, increases exposure risks for workers.13

A historical perspective: Understanding avian influenza through the years

Avian flu can be traced back to northern Italy in 1878, when a contagious disease of poultry with a high mortality rate was described, and then referred to as “fowl plague.” It was eventually determined that the “fowl plague” described was caused by a virus, which in 1955 was determined to be a type A influenza virus. In 1971, influenza viruses were originally classified based on the antigenic properties of their structural and surface proteins nucleoprotein hemagglutinin and neuraminidase proteins, as well as the species of origin. In 1981, the name “fowl plague” was officially replaced with avian influenza at the First International Symposium of Avian Influenza.

According to Justin Brown, DVM, PhD, a wildlife veterinarian with the Pennsylvania Game Commission in State College, Pennsylvania, the disease has historically remained within wild birds—mostly waterfowl, shorebirds, and gulls. However, the virus has recently been infecting new avian species, giving it the disease the potential to spread over into other avian hosts, like poultry.

“When you have those high-path influenza viruses that emerge, the way that works is they have those low-path viruses that are circulating in the wild bird reservoir. If those viruses are an h5 or an h7 subtype, and they spill over into the poultry, they can then adapt specifically to poultry and mutate to become highly pathogenic. So, in the field, it often shows up, at least in poultry settings, that you have this acute and massive mortality,” said Brown.

“What has happened historically was that the virus originated in wild birds, was transmitted to poultry, adapted to poultry, and then became a high-path variant, right? So, the way avian influenza typically transmits in wild birds is a fecal-oral route. Often fowl don’t get very sick with these low-path viruses, they do transmit low-path viruses very effectively,” Brown explained.

Brown also explained besides the spread through water, the virus also spreads between species when a bird defecates, and a different species comes in direct contact with that fecal matter. The latter may occur with animals like cats outdoors as well as humans that unknowingly step in feces and bring it into their homes.

As the threat of infectious diseases continues to grow, veterinarians and animal health experts are facing an increasing challenge in managing species that may serve as reservoirs for transmission. Although the traditional focus for control of avian influenza has been on species like waterfowl and gulls, the list of potential carriers is expanding to other animals that are highly susceptible to infection. This list includes felines. Brown stated that ensuring separation between naive host species and known reservoirs remains a key strategy.

“The real challenge is that we’re seeing more and more species that probably are going on that potential carriers’ list. Before we focus on waterfowl and goals for controlling the spread of avian influenza. Now our focus expands to new species that we know are reservoirs. Now you’ve got a whole other group of animals that may fit that category, but I still think an important group would be your waterfowl [and] your gulls. Those are still species that can be infected, can transmit avian influenza, in some cases, without clinical signs,” Brown said.

“I think now you have to look at a lot of the other species, whether it is…some of your wild carnivores that we know can be infected and things like that. I think if you’re dealing with a susceptible species, [such as] cats, which are going to be an increasing challenge because they are highly susceptible to infection… I think trying to keep separation from those known reservoirs is going to be your best route. That’s easier said than done however in some systems,” he continued.

With the rise in cases infecting novel species, Brown discussed that avian influenza has the potential to change the way veterinary teams look at sick patients in their clinics. Prior to the past 2 years, if a feline practitioner had a patient that was presenting with avian influenza symptoms, such as being acutely neurologic, they would have a long list of diseases to check again before coming to avian influenza, and dogs might not even have it on their list of differentials at all. What was once uncommon events within small animal practices has since become more widespread, leading professionals to take a closer look at other external factors for patients.

“Avian influenza virus is widespread in wild birds. Nothing adapts and changes like the flu. Every year in the flu world, we are like, ‘Well this is something new we haven’t seen before, or this is something we didn’t think would happen.’ The virus is changing, and so I think it’s important that you understand the current situation and sort of keep updated on what’s happening with the virus,” Brown said.

“A lot of times, we learn something about a pathogen, and then we sort of keep the old textbook version of it in our mind. This is one that I think, because of how much is changing, is important that you keep not only an understanding of influenza and the pathogen itself but also the current status of disease. Because it wouldn’t surprise me if in 1, 2, [or] 3, years, we see a different situation and a different tweak on the avian influenza outbreak which is happening now,” he said.

As H5N1 poses a multifaceted threat to both animal and human health, ongoing research, surveillance, and public health preparedness strategies are essential. The adaptability of the virus calls for a proactive approach to disease management, ensuring a coordinated response to safeguard public health.

References

1. How CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation. CDC. October 19, 2024. Accessed October 29, 2024. https://www.cdc.gov/bird-flu/h5-monitoring/index.html
2. CDC A(H5N1) Bird Flu Response Update October 18, 2024. CDC. October 18, 2024. Accessed October 29, 2024. https://www.cdc.gov/bird-flu/h5-monitoring/index.html
3. CDC Confirms Human H5 Bird Flu Case in Missouri. CDC. September 6, 2024. Accessed October 29, 2024. https://www.cdc.gov/media/releases/2024/s0906-birdflu-case-missouri.html
4. CDC Report on Missouri H5N1 Serology Testing. CDC. October 24, 2024. Accessed October 28, 2024. https://www.cdc.gov/bird-flu/spotlights/missouri-h5n1-serology-testing.html
5. First presumed human infections of avian influenza under investigation in Washington state. WSDH. October 20, 2024. Accessed October 29, 2024. https://doh.wa.gov/newsroom/first-presumed-human-infections-avian-influenza-under-investigation-washington-state
6. CDC A(H5N1) Bird Flu Response Update October 11, 2024. CDC. October 11, 2024. Accessed October 29, 2024. https://www.cdc.gov/bird-flu/spotlights/h5n1-response-10112024.html
7. Khurana, S., King, L.R., Manischewitz, J. et al. Licensed H5N1 vaccines generate cross-neutralizing antibodies against highly pathogenic H5N1 clade 2.3.4.4b influenza virus. Nat Med. Published July 16, 2024. Accessed October 29, 2024. https://doi.org/10.1038/s41591-024-03189-y
8. CDC. Interim Guidance on the Use of Antiviral Medications for Treatment of Human Infections with Novel Influenza A Viruses Associated with Severe Human Disease. Updated May 24, 2024. Accessed October 29, 2024. https://www.cdc.gov/bird-flu/hcp/novel-av-treatment-guidance/index.html
9. Caserta LC, Frye EA, Butt SL, et al. Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle. Nature. Published online July 25, 2024. doi:10.1038/s41586-024-07849-4
10. CDC. Considerations for Veterinarians: Evaluating and Handling of Cats Potentially Exposed to Highly Pathogenic Avian Influenza A(H5N1) Virus. Avian Influenza (Bird Flu). Published June 24, 2024. https://www.cdc.gov/bird-flu/hcp/animals/index.html
11. Highly pathogenic avian influenza A(H5N1): Guidance for veterinarians assessing HPAI H5N1 in domestic felines. Colorado Department of Public Health and Environment. Accessed August 15, 2024. https://d3cban8v3q1zt4.cloudfront.net/app/uploads/20240809113317/Guidance-for-Veterinarians-assessing-H5N1-HPAI-in-domestic-felines-2.pdf
12. Genetic Tests Are Detecting Prevalence of Bird Flu Virus in US Wastewater and Allowing Officials to Track its Spread. DarkDaily. October 8, 2024. Accessed October 29, 2024. https://www.darkdaily.com/2024/10/07/genetic-tests-are-detecting-prevalence-of-bird-flu-virus-in-us-wastewater-and-allowing-officials-to-track-its-spread/
13. Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024. Emerging Infectious Diseases. Volume 30, Number 7—July 2024. Accessed October 29, 2024. https://wwwnc.cdc.gov/eid/article/30/7/24-0508_article