H5N1 Bird Flu: What You Need to Know

In September, the Centers for Disease Control and Prevention (CDC) announced the first human case of avian influenza A(H5) in the United States without known exposure to an infected animal. Additionally, no exposure to a sick person was reported.
This followed 13 cases reported since April in 2024: four in dairy workers reported across three states (Texas, Michigan, and Colorado) and nine in poultry workers from two facilities in Colorado. An additional 13 cases of avian influenza A(H5) in dairy farm workers in California were also recently confirmed by CDC. A previous case of A(H5) was reported in Colorado in 2022. 
Medscape spoke with Tim Uyeki, MD, MPH, MPP, Chief Medical Officer for the Influenza Division at the National Center for Immunization and Respiratory Diseases of the CDC, about the current H5N1 situation and what the CDC is doing to monitor its activity.
We also spoke to Cara Drehoff, DVM, MPH, Epidemic Intelligence Service Officer at the CDC, who headed the response to a cluster of cases of poultry workers in Colorado.
Text has been edited for length.
Uyeki: Twenty-seven human cases of avian influenza A(H5) were identified in the US from the end of March through October 18, 2024. This includes 17 cases in dairy cattle workers in four states, nine cases in poultry workers in one state, and one case that was identified in a person without occupational exposure in another state. Nearly all received oseltamivir treatment, and all recovered. 
2024 is the first time that dairy cow-to-human transmission of highly pathogenic avian influenza A(H5N1) virus has been reported; to date, these sporadic cases have been identified in workers exposed to infected or presumably infected cows in Texas, Michigan, Colorado, and California in association with the ongoing multistate outbreak of A(H5N1) virus among dairy cattle. Sixteen of the 17 cases to date in dairy farm workers had conjunctivitis, and one case had acute respiratory illness symptoms. None of these cases required hospitalization; they all had clinically mild illness, all were treated or offered oseltamivir treatment, all recovered, and no transmission to close contacts was identified.
The nine cases in poultry workers were associated with exposure to A(H5N1) virus during outbreaks among chickens at two commercial egg-laying facilities in Colorado. All of these poultry workers identified with avian influenza A(H5) virus experienced conjunctivitis, a few also had respiratory symptoms, none were hospitalized, and all recovered. No secondary transmission to close contacts was detected. 
The CDC also confirmed a case in Missouri who was hospitalized with atypical symptoms. Investigations did not identify any known exposures to animals or to a sick individual, and no secondary transmission to close contacts was identified. A(H5N1) virus was confirmed in a respiratory specimen after the patient had been discharged home. 
All of these human cases have been confirmed or are presumed to be associated with one particular genetic clade of the virus, clade 2.3.4.4b. 
Uyeki: There continue to be human cases of avian influenza A(H5N1) reported sporadically in other countries. Historically, since 1997, there have been 935 cases reported from 24 countries, with a case fatality proportion of approximately 50%. Although no severe cases have been identified in the US to date, severe disease or critical illness, including with a fatal outcome, has been reported in other countries with A(H5N1) virus, clade 2.3.4.4b, infection. There have been 10 cases reported in Cambodia this year to date. These cases have occurred in rural villagers with direct and close unprotected exposure to backyard poultry that were sick or had died. Some of these cases experienced critical illness, and two died. These cases were associated with a different but related genetic clade of A(H5N1) virus, called 2.3.2.1c.
There was also a case reported earlier this year in Australia of a child who experienced critical illness but survived. The family had returned from travel to India, and the child’s illness was caused by infection with a different but related genetic clade of A(H5N1) virus called 2.3.2.1a that is circulating among poultry in India.
Uyeki: Our assessment is that in the US, as well as globally, the public health threat of A(H5N1) viruses is currently low. However, people who work with infected animals, such as poultry and dairy cows in the US, are at increased risk for exposure to and infection with A(H5N1) virus. It would not be surprising if additional sporadic human cases are identified in persons with occupational exposure to infected animals (eg, poultry or dairy cattle) in the US if recommended personal protective equipment is not utilized. Although severe human illness associated with A(H5N1) virus infection has not been identified in the US to date, sporadic cases of severe pneumonia might be identified in the future, such as has occurred in many other countries. 
People who have nonoccupational exposure to infected birds, poultry, wild birds, or other infected animals may also be at higher risk for infection in the US and worldwide. Historically, many human A(H5N1) cases have occurred in rural areas in other countries after unprotected exposures to sick or dead backyard poultry. 
Ongoing surveillance of A(H5N1) viruses, as well as other novel influenza A viruses of animal origin, such as other avian influenza A viruses and swine influenza A viruses that have infected people, is critical to assessing the risk to public health. Because A(H5N1) viruses continue to evolve in unpredictable ways, the threat that these viruses pose to public health could increase in the future. 
Uyeki: Globally, over the past 2 years, we’ve seen spillover of A(H5N1) viruses from wild birds to infect many kinds of mammals in many regions of the world. This includes A(H5N1) virus infections of a wide range of very small to very large mammals, including both wild and farmed terrestrial as well as wild marine mammals, resulting in high mortality. In contrast, dairy cows that are infected don’t tend to get very sick or might have infection without apparent signs of illness, but some can display some signs of infection, such as reduced appetite, nasal discharge, dehydration, and a substantial drop-off in milk production, but can recover. High levels of A(H5N1) virus are found in raw cow milk from acutely infected dairy cows. 
The concern is that if A(H5N1) viruses adapt to spread and become established among mammals, that might increase the risk to public health. A(H5N1) viruses bind to receptors present in the respiratory tract and gastrointestinal tract of birds and are excreted in their feces. In humans, the receptors for these A(H5N1) viruses are not very prevalent in the upper respiratory tract but are more abundant in the lower respiratory tract and on conjunctival tissues. It is believed that one of the conditions, although not the only factor, for A(H5N1) viruses to have increased potential to spread from infected animals to people and among people is that the viruses need to be able to bind efficiently to receptors that are prevalent in the human upper respiratory tract, and this has not been observed to date. 
Because A(H5N1) viruses, like all influenza A viruses, are dynamic and continually evolving, ongoing surveillance of these viruses in wild birds, poultry, farmed and wild mammals (terrestrial and marine mammals), dairy cows, and any other infected animals is critical to monitoring the public health threat. In people who are infected, in addition to assessing the epidemiology and clinical characteristics, we continue to analyze and characterize these viruses to assess the risk for transmission, pathogenesis, susceptibility to antivirals, antigenic similarity to candidate vaccine viruses, and other characteristics. It is very important to be vigilant, to enhance surveillance, and for public health to work closely with our animal health partners in a One Health response to A(H5N1) viruses in the US and worldwide. 
Drehoff: In July 2024, the Colorado Department of Public Health and Environment responded to two poultry facilities that had detected highly pathogenic avian influenza in their poultry. Both facilities were egg-layer facilities that had over a million birds. When we detect this virus in birds, they have to be depopulated, and a lot of these facilities will bring in large groups of contract workers to accomplish that task.
We were notified that some of the workers at the first facility had some symptoms that were consistent with influenza A, which was concerning because of their potential exposure to the A(H5N1) virus. We ended up conducting a series of site visits to both facilities to screen workers for symptoms, offer clinical testing, and provide empirical treatment with oseltamivir owing to exposure. In total, we talked to over 600 workers across the two facilities and identified 109 who reported symptoms. Of those workers, nine tested positive for influenza A(H5) virus. The first facility had six cases, and the second facility had three cases. 
Drehoff: This is actually the first cluster that we’ve seen associated with an occupational poultry exposure in the US. Overall, these Colorado cases were similar in terms of animal exposure and clinical presentation, but this is really the first time that we’ve seen a group of cases present after an occupational poultry exposure to avian influenza A(H5) virus. 
Drehoff: Luckily, the disease was very mild. All nine cases reported conjunctivitis, and then some reported other systemic symptoms, such as fever or some mild respiratory symptoms. All of these workers recovered in a few days. That’s the important takeaway here: ’We’re not seeing severe disease and there were no hospitalizations required. 
We didn’t see any evidence of human-to-human transmission, and all of the workers who tested positive had been handling sick or dead birds.
Drehoff: We’re still looking further into exactly how these workers were exposed. We did ask workers about PPE use, such as masks and goggles. We were concerned that the heat wave in Colorado might have impacted PPE use and the ability of workers to keep that PPE on when it was so hot out. We’d like to connect with the industry and occupational health to look at that a bit further and keep these workers protected in the future.
Drehoff: I do think there are some things that we did well. First, we were really cognizant of the cultural and language needs of the workforce. A lot of these contract workers were Spanish-speaking migrants. We made sure that we had multiple bilingual responders available at each visit who really helped facilitate communication, testing, and treatment for these workers.
I’ll also say that the scale and speed of the response were commendable — we did respond on the ground the day that symptoms were reported. We had a multidisciplinary team come in almost every day or every other day at these facilities to be able to organize these logistics and systematically screen workers and offer care on site where workers might not otherwise have access to that kind of care.
Drehoff: I think there’s a lot that we learned that we hope we can take into our next response to help inform prevention and future efforts. So much of this is about building relationships with our agriculture and industry partners and making sure that we have communication channels when we need to conduct outreach to workers. Strengthening our cultural navigation and Spanish-speaking staff to ensure that we have resources available to meet specific needs across different groups of people and communities is also important moving forward.
Drehoff: We are still investigating why we saw this cluster of cases. Is it the virus? Is it PPE use? We are also trying to take what we learned and remain prepared for future occurrences of this, especially as we enter migratory bird season and might expect to see additional poultry facilities affected. That really comes down to working through lots of logistics; how we can build field teams and conduct these screening visits, acquiring oseltamivir, and trying to work through decisions of when it is appropriate to do empirical treatment vs postexposure prophylaxis. We also want to build our relationships with the agricultural industry and our regulatory agricultural partners, so that we’re always on the same page and can approach these responses in a collaborative way.
Uyeki: As part of enhanced surveillance, the CDC recommended that any detection of influenza A virus in a respiratory specimen from a human patient across any healthcare setting in the US be subtyped. This will determine whether the virus is a seasonal influenza A virus subtype, such as A(H1N1)pdm09 virus, or A(H3N2) virus. If the respiratory specimen cannot be subtyped, then it needs to be tested further, including for A(H5) virus.
That’s exactly what happened in the Missouri case. This person had chronic medical conditions and was hospitalized with gastrointestinal symptoms, chest pain, and no respiratory symptoms — atypical for seasonal influenza or A(H5N1) virus infection — and no occupational exposure to animals. Although A(H5N1) was not suspected, as part of the workup, influenza A virus was identified in a single upper respiratory tract specimen collected on admission at the hospital, oseltamivir treatment was started, droplet precautions were implemented, and the specimen was sent to the Missouri State Public Health Laboratory for influenza A virus subtyping. It was negative for A(H1) and A(H3) but was presumptively positive for A(H5). That upper respiratory tract specimen was sent to the CDC after the patient had recovered from a brief hospitalization and was discharged home, and my colleagues confirmed A(H5N1) virus. I would note that a very low level of A(H5N1) viral RNA was detected, suggesting that it was not replicating, and virus was not able to be isolated. Therefore, in that respiratory specimen, there was no evidence of infectious virus, suggesting that during the hospitalization, the patient was unlikely to be contagious to others. Only partial sequencing of A(H5N1) viral RNA from the respiratory specimen was possible, and these results suggested that the virus was a highly pathogenic avian influenza A(H5N1) virus, clade 2.3.4.4b. This is the same clade of A(H5N1) virus that has been circulating among wild birds and infecting poultry, dairy cattle, and other animals in the US Because the patient did not have any exposure to animals or to sick individuals prior to becoming ill, the source of A(H5N1) virus infection in this patient is unknown.
Since February 2024, there have been more than 53,000 respiratory specimens collected from people in the US using a protocol that would have detected an A(H5) virus, and this is the only patient who was identified through such influenza testing to date. What we can say is that we haven’t identified any other cases in hospitalized patients in the US — except for this Missouri case. [The Missouri case] raises a lot of questions, but there’s been no indication of community transmission or any secondary spread from this patient. It appears that the threat to public health is low.
Uyeki: There are some human cases of A(H5N1) that have occurred historically in other countries in which the source of the virus was not identified. That has also happened in animal-to-human transmission of other novel influenza A viruses. For example, sometimes we will identify what is referred to as a ‘”variant influenza A virus of swine ’origin” in a patient’s respiratory specimen, but the patient didn’t have any known exposure to pigs. 
The source of exposure and infection is not always identified for every case, but we don’t think there’s any ongoing public health risk. We will continue to work closely with our local and state health partners on enhanced surveillance for influenza A viruses and novel influenza A viruses. We will also continue to assess other components of our surveillance, including looking at emergency department visits, hospitalizations, and other illness data as well as wastewater surveillance for influenza A viruses.
Uyeki: When a healthcare provider is evaluating a patient who might have acute respiratory symptoms or conjunctivitis, it’s important to ask about any exposure to animals in the 10 days prior to symptom onset. This includes wild birds, poultry, dairy cows, or other mammals, particularly those that were sick or died. For example, there have been cats infected with A(H5N1) virus that exhibited neurologic signs of illness and then died.
Clinicians should also ask patients about consumption of raw milk, raw milk products, or uncooked poultry products.
Clinicians should also ask if a patient had any exposure to someone who was a confirmed case of novel influenza A virus infection to explore the potential for human-to-human transmission. We haven’t identified any secondary transmission of A(H5N1) virus in the US, and limited, nonsustained human-to-human transmission of A(H5N1) virus has not been reported globally since 2007, but we always need to investigate this possibility because these viruses are dynamic, and they could evolve to become a greater public health threat in the future.
If there is a relevant exposure to animals and clinical signs and symptoms of conjunctivitis, and/or acute respiratory symptoms are present, then influenza testing should be done. Influenza A subtyping should be done if influenza A testing is positive. If there’s high suspicion of exposure to sick or dead poultry, mammals, or dairy cattle, then the state health department should be notified. Clinical specimens should be sent to a public health laboratory for specific influenza A testing and capacity for A(H5) testing.
Patients with relevant exposures and clinical signs and symptoms of influenza should be started empirically on oseltamivir treatment as soon as possible; don’t wait for the results of influenza testing. Then, if the patient tests as presumptive positive for influenza A(H5) at the state level, the patient needs to be isolated, investigations need to be done, and the specimen(s) need to be shipped to CDC for confirmatory testing. Close contacts of a case need to be identified and followed up and started on post-exposure oseltamivir prophylaxis as soon as possible, especially if A(H5N1) virus infection is confirmed at CDC. 
Uyeki: People should avoid direct and close exposure to sick or dead animals, especially wild birds or poultry, or to dairy cattle suspected or known to be infected with A(H5N1) virus, period. Avoid touching or consuming raw milk or raw milk products, especially from animals with confirmed or suspected A(H5N1) virus infection.
People who might have occupational exposure to suspected or confirmed A(H5N1) virus–infected animals, such as dairy cattle or sick or dead poultry, should utilize recommended PPE, including an N95 respirator, eye protection such as goggles or a face shield, a protective gown, and gloves.
Additional prevention guidance is available on the CDC website, including PPE recommendations for workers. 
H5N1 vaccine is not currently available for anyone. However, as part of routine, ongoing pandemic influenza preparedness, the CDC is always working on developing candidate vaccine viruses to match the evolution of A(H5N1) viruses of highest public health concern. Currently, we have H5 candidate vaccine viruses that are a good match for the A(H5N1) viruses circulating in poultry and in dairy cattle in the US. 
We believe that threat to the public is low at this time, but if the public health threat were to change and vaccines were needed to go into production, these H5 candidate vaccine viruses have already been made available to manufacturers.
There are also some H5 vaccines in the Strategic National Stockpile that could potentially be used if there was indication that an influenza pandemic was starting, but again, there’s no indication that the public health threat is increased at this time. 
 
Public Information from the CDC and Medscape