A guide to vaccinology: from basic principles to new developments
How Deadly Is Bird Flu In Humans? What We Know As US Confirms First Death
Amid an ongoing outbreak of bird flu among poultry and dairy cattle across the United States, the country has recorded its first human death due the virus known as avian influenza A or H5N1.
On Jan. 6, state health officials confirmed that a person in Louisiana died after being hospitalized with a severe case of highly pathogenic avian influenza (HPAI) bird flu, according to a release from the Louisiana Department of Health.
The patient contracted the virus after coming into contact with non-commercial backyard flocks and wild birds, officials said. It was the first human case of bird flu linked this type of exposure and the first instance of severe illness in a human caused by H5N1 in the U.S.
Since 2024, there have been 67 human cases of H5N1 confirmed in the U.S, according to the U.S. Centers for Disease Control and Prevention. The vast majority have been among farm workers who had exposure to commercial poultry or dairy cattle, and cases have been mild. Most were treated with flu antivirals and fully recovered.
H5N1 is not new; it spreads naturally among wild birds and has caused outbreaks in poultry and sporadic human cases since 1997.
Although the threat to the public remains low, the CDC says, the fatal case in Louisiana raises concerns about H5N1 in humans.
How deadly is bird flu in humans?Since 2003, 954 confirmed cases of human H5N1 have been reported to the World Health Organization, and about half of those people have died. The case fatality rate is approximately 52%, per the CDC.
The countries reporting the highest number of human bird flu deaths are Indonesia, Egypt, Vietnam, Cambodia and China.
The case fatality rate varies by strain of bird flu. H7N9, another type of bird flu known to infect humans, has a lower fatality rate of about 40%, research shows.
"While tragic, a death from H5N1 bird flu in the United States is not unexpected because of the known potential for infection with these viruses to cause severe illness and death," the CDC in a statement on its website.
However, many experts say the H5N1 case fatality rate — which estimates the proportion of deaths among people diagnosed — has some caveats. "We have to look at (these numbers) carefully," says Dr. William Schaffner, professor of infectious diseases at Vanderbilt University Medical Center, tells TODAY.Com.
The case fatality rate is calculated by dividing total number of reported deaths by the total number of confirmed cases of H5N1. The resulting number could potentially be an overestimate given that mild cases of H5N1 can go undetected and unreported.
How deadly bird flu is in humans may depend on a number of other factors, says Schaffner. These include the amount of virus a person is exposed to, their underlying health status and access to medical care, such as antivirals.
"The people who have died (from H5N1), many of them are farmers who live very closely with their poultry — their ducks, chickens, geese — so they get a big dose (of the virus)," says Schaffner.
Similarly, the Louisiana patient had close contact with backyard birds and likely got a large dose, Schaffner suspects. "That, in combination with the fact that they were older and had chronic underlying illnesses, led to a very serious infection," he adds.
Bird flu deathsSo far, the Louisiana patient is the only person known to have died from H5N1 bird flu in the U.S. This was the first death due to the virus in the country, and the second human death from avian influenza recorded in North America.
Last spring, a 59-year-old man in Mexico died from another strain of bird flu, H5N2, the first confirmed human case of this strain globally, according to the WHO. The man also had underlying conditions and died after developing a fever, shortness of breath, diarrhea and nausea. He had no known contact with sick animals, the WHO said.
In comparison, seasonal influenza causes an estimated 4,900 to 51,000 deaths every year in the U.S., according to the CDC.
Bird flu symptoms in humansBird flu symptoms in humans range from mild to severe. Signs and symptoms of H5N1 may include:
In severe cases, bird flu can lead to complications such as pneumonia or respiratory failure, per the CDC.
So far, nearly all of the recent human H5N1 cases in the U.S. Have been mild, and most people experienced upper respiratory symptoms or pink eye, TODAY.Com previously reported.
In August, a person in Missouri was hospitalized with H5N1 bird flu and recovered after being treated with antivirals. The patient, who had underlying medical conditions, had no known exposure to sick animals, the CDC said on Sept. 6.
Additionally, a 13-year-old girl in Canada became critically ill last fall after contracting H5N1, the country's first human case of bird flu. The source of exposure is still unknown.
Although most of the human bird flu cases in the U.S. Have not resulted in serious illness, scientists are working to understand bird flu in humans.
Should I be worried about bird flu?Addressing the public health risk of bird flu for humans, WHO spokesperson Dr. Margaret Harris said at a press briefing on Jan. 7: "We are concerned, of course, but the risk to the general population ... Still remains low."
People who have close contact with infected birds or animals, either through their job or recreationally, are at higher risk of contracting H5N1, per the CDC.
So far, no person-to-person transmission of H5N1 has been detected, per the CDC, but there are concerns about the virus mutating or combining with seasonal flu strains to do just that.
"There were mutations in that (Louisiana) patient that could make it more susceptible to doing human-to-human transmission," NBC News medical correspondent Dr. John Torres said in a TODAY segment aired Jan 7.
However, a CDC analysis suggests these mutations occurred inside the patient while they were infected, and they were not found in poultry, making it less of a concern.
According to experts, it's unlikely that this H5 bird flu strain would lead to a pandemic because it currently doesn't have the ability to spread efficiently between people, TODAY.Com previously reported.
"This current bird flu virus has been around and ... Fortunately it has still has not picked up this genetic capacity to spread readily from person to person," says Schaffner. "Could it tomorrow? Yes, but it hasn't yet."
Scientists are closely monitoring bird flu's spread.
How to protect against bird fluAvian influenza can spread from infected birds to humans through direct contact, via contaminated environments or through an intermediate host, such as a cow. People become infected when H5N1 virus particles get into their mouth, nose, eyes or are inhaled. (You cannot get bird flu from eating an infected bird or eggs, as long as the food is properly cooked.)
The risk of humans getting bird flu is still low, but you can take the following steps to lower your risk:
How Effective Is The Flu Shot This Year? The Latest Data Shows Surprising Results
Every fall and winter, medical professionals preach the same message: Get your flu shot. While getting the flu shot always makes it less likely to get hit hard by the flu, its efficacy fluctuates. Some years the flu shot offers more protection than other years.
Now that we're well into flu season (widely considered to be between December and February), you may be wondering just how effective this season's flu shot is proving to be. Well, the latest data is out—and it may surprise you. Here, infectious disease experts offer up their insight into the data and also give the verdict on if it's too late to get the flu shot this season if you haven't gotten it already.
Related: Do You Have the Flu? Here's Everything You Need To Know About Navigating Symptoms and Treatment
Why Flu Shot Efficacy Changes Each YearSimilar to how there are different strains of COVID (like Omicron and XEC), there are different strains of the flu. There are four different types of flu viruses: A, B, C and D. Different strains circulate each year. The World Health Organization monitors which strains of the virus circulate all over the world and then recommends which strains should be covered by the annual flu vaccine.
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"Flu vaccine efficacy varies year to year, but it typically ranges between 40 to 60%. Year to year, the effectiveness of flu vaccines depends on the similarity of the vaccine viruses to the circulating virus," says Dr. Minji Kang, MD, an infectious disease expert at UT Southwestern.
Related: Here's What Flu Symptoms Look Like Day by Day
Dr. Sanjiv Shah, MD, MPH, an infectious disease specialist and the chief medical officer at MetroPlusHealth, says that reports of how effective the flu vaccine is each year are based on comparing people who seek medical care for respiratory illness lasting less than one week and identifying those who test positive for flu with those who test negative and comparing how often each had received that season's flu shot. "The reports vary from year to year based on which communities are studied, how well the flu strains that circulate match the components in the vaccine and social and underlying health factors of those studied," he says.
Dr. Shah explains that the flu shot typically contains up to four different inactive strains covering the two main types of flu: A and B. Getting the flu shot, he says, does not mean someone gets the flu. This is because the virus in the vaccine is inactive.
To protect people going into flu season, Dr. Shah says that the composition of the flu vaccine has to be set in place by February to have enough vaccine produced to start giving out doses in the fall. "This requires a scientific crystal ball because the virus can undergo mutations that may allow some strains to escape the vaccine," he says.
Related: Roll up Your Sleeves! These Are the 10 Best Ways To Prevent the Flu
How Accurate Is the Flu Shot This Season?With all of this in mind, how accurate is the flu shot this year? Dr. Shah says that data analysis is still very early (flu season is still going on, after all), but in December the CDC reported on data collected since September 2024 to find out how accurate this year's vaccine is. The result: "56% of one community-obtained virus was similar to one component of the vaccine and 100% of a second flu virus was similar to a different vaccine component," Dr. Shah says.
This means that, as usual, getting the flu vaccine this year will likely reduce the risk of flu-related illnesses by 40% and reduce the risk of hospitalization by 60%.
Both doctors say that if you haven't gotten the flu shot yet this season, there is still time. "Rates [of people with the flu] are on the rise now and there is still time to get vaccinated if you have not done so yet to reduce your risk of getting the flu or if you do get the flu, reducing the risk of getting very sick or dying from it," Dr. Shah says. Dr. Kang adds to this, saying, "Flu shots reduce the severity of the flu for people, prevent hospitalizations and deaths, and reduce the number of people who get the flu."
If you haven't gotten the flu yet because you don't think coming down with the flu is "that bad," Dr. Kang says to reconsider. "It's important to note that the CDC estimates that the flu has resulted in between 100,000 and 710,000 hospitalizations and up to 51,000 deaths every year, especially older adults, young children and people who have chronic health conditions. Flu shots protect you and others," she says. So even if you don't want to get the flu shot to protect your own health, do it to protect others'.
Dr. Kang also specifies that getting the flu shot doesn't guarantee you won't get the flu. But it does mean that if you do get the flu, your symptoms will be less severe and you will recover faster. She also reiterates that you cannot get the flu from the flu shot because the vaccine uses an inactive virus. "Overall, reactions to the flu shot are mild," she says.
Even though flu shot efficacy fluctuates, both doctors say that it's absolutely worth getting every year. If you haven't gotten it yet, book a time to do so today.
Up Next:
Related: Here's How Long You Can Actually Expect the Flu To Last
SourcesHow Close Are We To The Avian Flu Outbreak Escalating Into A Pandemic?
Avian flu is rampant in poultry farms and in wild birds in the U.S. Every mutation brings the virus one step closer to the brink of human-to-human transmission, but predicting whether a virus will cross that threshold remains an uncertain science.
After at least 66 documented cases of humans infected with bird flu – which is surely an undercount — the first death was just reported. A 65-year old man with additional medical issues had been exposed to a combination of a backyard flock and wild birds. Ten states reported cases in the grim first week of the New Year.
As shown in the CDC's table below, at least two cases in the United States involved patients with no known exposure to animals, heightening concerns that a full-fledged pandemic marked by human-to-human transmission is increasingly possible.
Confirmed human case summary since 2024, by state and exposure source Exposure Source State Exposure Associated with Commercial Agriculture and Related Operations Other Animal Exposure† Exposure Source Unknown‡ State Total Dairy Herds (Cattle) Poultry Farmsand Culling Operations California 36 0 0 1 37 Colorado 1 9 0 0 10 Iowa 0 1 0 0 1 Louisiana 0 0 1 0 1 Michigan 2 0 0 0 2 Missouri 0 0 0 1 1 Oregon 0 1 0 0 1 Texas 1 0 0 0 1 Washington 0 11 0 0 11 Wisconsin 0 1 0 0 1 Source Total 40 23 1 2 66NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022. Louisiana reported the first H5 bird flu death in the U.S. Earlier this month.
†Exposure was related to other animals such as backyard flocks, wild birds, or other mammals ‡Exposure source was not able to be identified
Source: CDC: https://www.Cdc.Gov/bird-flu/situation-summary/index.Html
The H5N1 avian influenza virus, particularly a variant called 2.3.4.4b, has been steadily spreading across the globe since 2021. It has evolved to become capable of infecting a diversity of avian species, marine mammals, cattle, and even, occasionally, humans.
Throughout the U.S., almost a thousand dairy herds have been infected, and more than 130 million poultry have died. (Whenever infection is detected in poultry, the entire flock is culled.) The situation in California is dire. Since the first identification of three infected herds in the state in late August, authorities have found the virus in more than 70% of the state's 984 dairies, prompting Governor Gavin Newsom to declare an emergency on December 18th. Only last week, outbreaks were detected at three poultry operations in Maryland and Delaware, causing more than 500,000 chickens to be culled and leading to heightened concern among officials in the Washington D.C. Region.
Although no sustained human-to-human transmission has been documented, 66 human H5N1 cases have been diagnosed in the U.S. So far this year, and recent genetic studies reveal that the virus might be closer to achieving pandemic potential than previously thought. That would be extremely dangerous, given that infections of humans by previous variants have caused up to 30% mortality.
H5N1 first raised alarms in 1997 when it infected 18 people in Hong Kong, killing six. It has appeared on pandemic watchlists ever since, as researchers uncovered the mutations likely needed to spread efficiently among humans. These mutations involve changes in two viral components: the RNA polymerase, an enzyme that replicates, or copies, the virus's genome, and hemagglutinin, the protein that enables the virus to latch onto host cells. (During my laboratory days, I was the co-discoverer of the polymerase of the human flu virus.)
Recent studies have amplified scientists' concerns. A recent report from a research group at the Scripps Research Institute in California found that a single mutation in hemagglutinin — called 226L — was sufficient to allow the virus to bind more effectively to receptors in human airways. Scientists had previously believed two such mutations were necessary, but the discovery of this "shortcut" was alarming because it indicates that adaptation to humans is more advanced than previously predicted.
Canadian warning sign
The case of a Canadian teenager hospitalized with H5N1 last November offers new clues. The virus samples from the patient showed signs of a mutation in hemagglutinin, though not the feared 226L. This suggests that the H5N1 virus may already be "experimenting" with mutations that could eventually lead to human-to-human transmissibility.
The teenager's virus came from a bird strain that had undergone genetic mixing, or reassortment, of the eight RNA segments that comprise the flu virus' genome. In this way, the viruses acquired a new neuraminidase protein (the "N" in H5N1), which could make the strain more adaptable.
This is what the CDC reported on December 26 when news arose of the infected Louisiana patient who eventually died:
CDC has sequenced the influenza viruses in specimens collected from the patient in Louisiana who was infected with, and became severely ill from HPAI A(H5N1) virus. The genomic sequences were compared to other HPAI A(H5N1) sequences from dairy cows, wild birds and poultry, as well as previous human cases and were identified as the D1.1 genotype. The analysis identified low frequency mutations in the hemagglutinin gene of a sample sequenced from the patient, which were not found in virus sequences from poultry samples collected on the patient's property, suggesting the changes emerged in the patient after infection. (Emphasis added.)
The CDC analysis underscores why it is important to "flatten the curve" of infections in humans and animals in order to reduce the number of opportunities for the virus to mutate.
Numbers game
For a flu virus to succeed, its hemagglutinin (H) and neuraminidase (N) proteins must work in harmony. Hemagglutinin binds the virus to host cells, while neuraminidase detaches it, enabling the virus to spread. If the balance is off — too sticky or too loose — the virus fails to proliferate. In the bird strain that infected the Canadian teenager, a new neuraminidase might provide the flexibility needed for hemagglutinin to evolve toward enhanced human infectivity.
One unsettling possibility is that H5N1 already has the mutations needed to spark a pandemic, but its limited spread among humans has kept it in check. The more human exposures to the virus, the greater the chances it will find the right genetic combination.
The occurrence of mutations or advantageous reassortments is all a matter of probability, and the more infections that occur, the more virus replication there is, and the more opportunities for new, worrisome variants to appear that will be winners in Darwinian evolution's game of survival of the fittest.
(As mentioned above, that is why public health interventions should include "flattening the curve" of infections — to lower the probability of new, more dangerous variants appearing).
Where are we now? As Dr. Jeremy Faust, a Harvard Medical School physician, warns, "our current circumstance is akin to a game of Russian Roulette — and there have never been more bullets in the chamber."
Surveillance to track genetic changes of the virus is crucial. While the discovery that a lone 226L hemagglutinin mutation could be a potential single-step shortcut to human adaptation is alarming, it doesn't guarantee a pandemic. Other mutations — such as at certain positions in the polymerase — are likely needed to enable efficient human-to-human spread.
Preparing for the unknown
The case of H5N1 underscores a broader reality about pandemics: They are rare but not impossible. Each mutation brings the virus one step closer to the brink, but predicting whether a virus will cross that threshold remains an uncertain science.
As history has shown, the cost of underestimating a pandemic threat can be devastating. H5N1 may still be contained primarily within animals, but the steady march of new mutations is a reminder that nature can surprise us. Staying one step ahead of the virus could mean the difference between a close call and a global catastrophe.
An earlier version of this article was published by the Genetic Literacy Project.
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