Human H5N1 Bird Flu Cases in the United States

As of 12/2/2024, the CDC lists 57 human H5N1 cases in its official count.  This tally is very likely, if not certainly, an undercount. 

The official count of human H5N1 cases is likely low:

This official count of bird flu cases in the U.S. is very likely an underestimation.  Indeed, several occurrences have indicated that some presumed positive, or even positive cases subsequently discovered, are not included in the CDC’s list:

• The CDC count does not include the 8 presumably mild or asymptomatic cases of H5N1 found by serological testing.

• The CDC count does not include the second, strongly suspected, human case in Missouri, who was a close contact of the first case, although the route of infection may have been a common source for both people and not transmission by the first case.  To date, the public health authorities do not know how either person was infected.

• The CDC count does not include cases that were confirmed by state laboratories but not by the CDC.  These are referred to in a curious little footnote at the bottom of the CDC chart: “Additional cases meeting the Council of State and Territorial Epidemiologists (CSTE) probable case definition have been reported by states: 1 case with dairy cow exposure (CA), 3 cases with poultry exposure (WA). Confirmatory testing at CDC for these cases was negative.”

Recent human H5N1 cases included in the official count:

The last official total was 55 human cases.  On 12/2/24, the California Department of Health added 2 new human cases to the state’s total, bringing it up to 31.  These 2 cases from California have been added to the official CDC list, as the CDC’s FluView database indicates, identifying 2 new cases in dairy farm workers in California.  FluView also included a brief description of these new cases:

So things are clearly picking up on the bird flu front.  Only two months ago, California was investigating the first “possible” case of bird flu in that state. Fast forward to today, and there are now 31 human cases, all but 1 of which was linked with exposure to sick cows.  

The exception was the case identified on 11/19/24, in which a child from Alameda County tested positive for H5N1.  The child experienced “mild respiratory symptoms” and was not hospitalized.  The child had no known contact with an infected animal. There has not been any further information as to how this child was exposed to or infected with this bird flu virus.

Human Bird Flu Cases are Increasing:

The acceleration of human bird flu cases in California, the state with the most dairy herds infected, is alarmingly consistent with the acceleration of human cases in the United States.   

April 2022: 1 case

Prior to this year, the only human case of H5N1 in the U.S. was from April 2022 on a commercial poultry farm in Colorado.  The CDC reported on April 28, 2022, that a person involved in the depopulation of poultry infected with H5N1 had tested positive for the virus.  This was big news at the time, as it was the first human case of H5N1 in the U.S.  The case was very mild, as the person only reported experiencing fatigue.  According to the WHO statement on the case, the man developed fatigue on April 20, 2022 during his participation in slaughtering infected poultry from April 18 – April 22.  A respiratory sample was obtained on April 20 and testing was completed by the state laboratory on April 25 which showed positive influenza A infection.  The CDC confirmed H5 virus infection on April 27, with the subtype N1 subsequently confirmed.  

During this time, H5N1 infections had been confirmed in poultry flocks in at least 29 states, as well as wild birds in at least 34 states.  Interestingly, there was some uncertainty as to whether this was a proper case of bird flu or the result of “contamination” of the nasal passages without actual infection, but given the positive test result the CDC treated it as a true H5N1 human infection and the person was provided with oseltamivir.  This Colorado case was an outlier as there were no other cases reported, even amongst other people involved in the same culling operation on the same farm.  In total, 9 contacts of the positive case were tested and monitored, all of whom tested negative.  

Of note, in the press release announcing this human case, the CDC stated: “This one H5-positive human case does not change the human health risk assessment. CDC will continue to watch this situation closely for signs that the risk to human health has changed. Signals that could raise the public health risk might include multiple reports of H5N1 virus infections in people from exposure to birds, or identification of spread from one infected person to a close contact. CDC also is monitoring H5N1 viruses for genetic changes that have been associated with adaptation to mammals, which could indicate the virus is adapting to spread more readily from birds to people.”

April 2024 – Present: 57+ cases

Less than two years later, we are now at upwards of 50 human cases of H5N1 bird flu.  That’s unheard of for the United States.  At least it was, until dairy cattle became infected with the virus.  The dairy cattle outbreaks have facilitated spillover infections into farm workers at that human-animal interface.  We have also seen additional outbreaks in poultry, some of which have led to additional human cases from direct poultry exposure.

To date, the CDC officially lists 57 human cases of H5N1, all occurring in 2024. The first case was identified in April 2024, in a dairy farmworker in Texas.  Since then there have been (at least):

• 21 human H5N1 cases associated with exposure to infected poultry

• 34 human H5N1 cases associated with exposure to infected dairy cattle

• 2 human H5N1 cases with “unknown” exposure

H5N1 adaptation to mammals:

So is there evidence that the current clade of H5N1 is adapting to mammals, and possibly to humans?  Sequencing of some viruses from the 2024 dairy cattle outbreaks and related human H5N1 cases have found some genetic changes that are worth noting.  The virus from the first human case identified in 2024, the Texas dairy farm worker, carried two mutations associated with adaptation to mammals.  The PB2 E627K mutation is a known marker for increased replication in mammals and more severe disease.  The PA K142E mutation is associated with increased virulence in mammals when combined with PB2 E627K. Sequences from subsequent human cases showed some adaptations associated with reduced susceptibility of antiviral drugs.  The PA-I38M mutation, associated with reduced susceptibility to baloxavir, was found in a viral sample from 1 human case in California.  Additionally, H5N1 viruses from 3 human cases in Washington State carried the NA-S277N mutation which is associated with reduced susceptibility to oseltamivir.

Additionally, some studies have found some viruses sampled from the ongoing outbreaks in dairy cattle and associated human spillover cases to transmit between ferrets in the laboratory. In one CDC study, the Texas human H5N1 virus was found to spread to 3/3 direct contact ferrets and spread by respiratory droplets to 4/6 airborne contact ferrets.  According to the CDC: “The observed capacity of avian influenza A(H5) virus to transmit via respiratory droplets in ferrets has not been frequently reported in the past.”  I’ll say.  Another study using this same human virus found respiratory transmission between ferrets and found that the virus replicated in human lung cells in the laboratory.  In a study evaluating an H5N1 virus obtained from an infected dairy cow from a herd in New Mexico, that virus was found to bind to both avian and human receptors.

There does appear to be at least some sort of evolution going on here.  For an H5N1 virus to be able to bind to human a-6 receptors is very noteworthy.  It is one of the key considerations in weighing the risk to public health, as a virus cannot gain traction and spread amongst humans until it can efficiently infect and transmit between humans, and it can’t do that without binding to the human-style receptor.  This was only shown in one laboratory study and is certainly not the “norm” for this virus.  

But as H5N1 continues to make its way through dairy cattle herds across the United States, it will continue to infect humans that work closely with those infected herds.  It may also infect different species of wild birds that are in close proximity to these cattle herds, or poultry on the same farm, or any number of other livestock kept on the same farm.  There are many ways that this bird flu virus can continue to spread through different hosts.  As it does so, it will continue to change, to adapt, and one day we could find ourselves facing something that is more suitable for human infection and transmission.  

Until next time.