The Avian Influenza virus has now been circulating in the United States for months, infecting egg-laying chickens, dairy cows and other animals. Prices of eggs have risen, as millions of hens have been sacrificed to slow the spread of the virus. Post-COVID, we are concerned about the possibility of yet another epidemic: one caused by the Avian Influenza virus. In this guest commentary for the Jon Samet Report, Dr. Amesh Adalja, an infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security, provides an up-to-date perspective on avian influenza. Stay tuned to this unfolding and dynamic story. 

-Jon Samet

Avian Influenza: An Emerging Threat to People

by Dr. Amesh Adalja

Headlines in almost every state, almost every day, mention bird flu cases being diagnosed in cattle, wild birds, poultry, and even humans. How to process this information and understand what risk calculations you should make may seem a daunting task if you are trying to figure out how this could affect your day-to-day life. In the aftermath of the COVID-19 pandemic, we are all sensitized to the possibility of another pandemic.  

To understand the current human risk of bird flu in the United States, it is crucial to situate it within the broader context of influenza. 

Influenza basics 

The “flu” is an illness caused by a specific group of viruses (despite the fact that many people colloquially use the word “flu” to describe a large group of upper and lower respiratory illnesses). Influenza viruses are grouped into 4 groups (A-D) and cause a syndrome that includes cough, fever, muscle aches, congestion, and sore throat. A severe case of influenza can cause pneumonia, brain infection, and death. Even now, influenza kills tens of thousands of Americans annually and hospitalizes hundreds of thousands. Of the 4 groups of influenza viruses, it is influenza A that has caused pandemics, four over the last 110 years (1918, 1957, 1968, and 2009), including the most notorious and devastating--the 1918 Influenza Pandemic.  

Each pandemic was sparked by the emergence of a new version of influenza A to which the human population had no immunity.

The origins of influenza A viruses 

All varieties of influenza A viruses continuously and naturally circulate in waterfowl, including ducks, geese, and more. In this reservoir species, they don’t cause disease but when these viruses infect other avian species, such as poultry, they can cause severe disease. Ordinarily, avian influenza viruses are not readily able to infect humans and other mammalian species because they cannot attach to the key receptors on cells and initiate infection. However, through genetic mutations, some avian influenza viruses evolve that ability. Our usual seasonal influenza A viruses are descendants of avian influenza viruses that developed the capacity to efficiently infect humans and spread amongst them. The avian virus that caused the 1918 influenza pandemic is an example of an avian virus that found its way into humans and possessed the ability to prolifically spread. Another way that avian viruses acquire the ability to infect humans is by shuffling genetic material with other influenza A viruses in a human or other animals (notoriously pigs). In this process, genes are reshuffled and a hybrid virus may emerge that can attach to cells and infect humans. This phenomenon was responsible for the influenza pandemics that occurred in 1957, 1968, and 2009.

Potential severity and human transmission

Though the human immune system has experienced the influenza A viruses that it is exposed to year after year, it is not experienced with those that are significantly different from the seasonal versions. As such, a human population with immune systems new to a virus will be more susceptible to the virus and disease may be more severe. Many, but not all, avian influenza viruses are known to cause severe disease in humans.  

As mentioned earlier, avian influenza viruses are constrained by the differences between human and avian cells. These differences delimit their ability to spread amongst humans. The avian virus must have the ability to efficiently spread between humans if it is to cause a pandemic. One way this ability might evolve is through continual sporadic infections of humans or other mammalian species. Each infection puts evolutionary pressure on the virus to adapt to the new species. When the virus causing each human case of avian influenza is genetically characterized, it is these adaptations that are being assessed.  

Current U.S. situation 

Of the myriad avian influenza viruses that exist and have infected humans, it is H5N1 that is of specific concern in the U.S. currently. This form of avian influenza was first documented infecting humans in 1997 when a relatively small but deadly outbreak occurred in Hong Kong. Since that time, the virus has evolved and for the past several years a form of H5N1 (known as 2.3.4.b.b) has been infecting bird species worldwide. These infections have led to catastrophic losses of poultry due to the need to cull infected flocks, which has caused supply shocks to the egg industry and raised prices. The confinement of the issue to poultry had been the status quo until recent years when the virus began to find its way into many different mammalian species, including foxes, alpacas, cats, marine mammals, and most notably cows. 

From birds to cows 

The entrée of influenza A into the U.S. dairy cattle population was notable for several reasons. First, cows were not known to be susceptible to infection. When the virus spread from birds to cows, the crossover went unnoticed as the virus does not cause traditional influenza symptoms. Second, cryptic or silent, unnoticed spread from herd to herd (perhaps through contaminated milking equipment) was not noticed until the virus was in multiple herds in multiple states.  

The virus was detected in milk from infected cows and, as expected, pasteurization renders it inert. Thus, dairy products made from pasteurized milk are safe. However, unpasteurized milk, in vogue amongst certain segments of the population, is a risk for infection. Additionally, chicken products have been responsible for pet food-related outbreaks in cats. 

Starting from April 2024, human cases have occurred in dairy cattle workers involved in milking. These cases have primarily manifested as mild eye infections. Cases have also occurred in U.S. poultry workers.  

It has been difficult to gain a handle on the dairy cattle farm outbreaks as many farmers have been reticent to have comprehensive testing performed on their farms. Dairy cattle are a major economic good and a farm engulfed in an outbreak will suffer financial consequences. The resulting tension between public health agencies and dairy farmers has made it difficult to adequately track the dairy cow epidemic. 

Mostly mild cases so far 

Historically H5N1 cases have been very severe with case-fatality ratios reaching to 50%. However, in the U.S., only one fatal case has occurred to date and serious illness is the exception. This somewhat paradoxical situation may be the result of the specific substrain of H5N1 involved, the main mechanism of exposure (eyes in the dairy cattle workers), the health status of those infected, or some combination of factors. The occurrence of a fatal case in the U.S. and of a severe case in Canada underscores that there remains potential for severe disease. In these instances, it is unclear why severe disease occurred and both cases were related to exposure via a bird -- and not a cattle strain.

Vaccine Production

Due to prior threats of H5N1, vaccines for human use have been stockpiled. Though not matched exactly to the currently circulating strain of H5N1, they are expected to provide some protection against severe disease. More closely matched vaccine strains are being produced and stockpiled and a cattle vaccine is also being pursued. One reason why a widespread vaccine program hasn’t been pursued is because severe human disease has been rare. However, it is arguable that a vaccination program would be beneficial for those in high-risk occupations such as dairy cattle and poultry workers as well as veterinarians.  

Continued monitoring is critical 

The H5N1 influenza A avian influenza outbreak is a pressing challenge for public and animal health authorities. The virus is likely now widespread in dairy cattle and will be difficult to eliminate. Human cases, however, have almost all been mild and treated with standard antiviral therapy. The ability of the virus to spread between humans is severely limited; however, it will remain critical to monitor the virus for the acquisition of characteristics that may remove that barrier. Even if this strain of avian influenza does not possess the characteristics to cause a pandemic, the emergence of the virus in multiple mammalian species is a trial run for the eventual appearance of an avian influenza virus that will.

Dr. Amesh Adalja is a senior scholar at the Johns Hopkins Center for Health Security and a practicing infectious disease, critical care, and emergency medicine physician in Pittsburgh. 

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This article is part of a monthly column, The Jon Samet Report, on the biggest issues facing us today in public health, written and curated by the former dean of the Colorado School of Public Health, Jon Samet, a pulmonary physician and epidemiologist, and Professor of Epidemiology and Occupational and Environmental Health. Dr. Samet is a global health leader, shaping the science and conversation on issues ranging from tobacco control to air pollution to chronic disease prevention and more. Each month he shares expert insights on public health issues from local to global.