Summary of H5N1 Seroprevalence Studies

Summary

What CDC knows

CDC has been tracking highly pathogenic avian influenza A(H5N1) viruses ("H5N1 bird flu") globally for more than 26 years. A lot of data have been collected to inform ongoing risk assessments. Overall, human infections with H5N1 bird flu viruses have been relatively rare and sporadic, despite the fact that these viruses have spread widely in wild birds worldwide and caused poultry outbreaks in many regions. In addition to public health surveillance for new human cases, studies that look at the prevalence of neutralizing antibodies to H5N1 bird flu viruses in people's blood can help inform the public health risk of these viruses. A review of these studies supports the fact that H5N1 bird flu viruses have not spread easily to infect people in the past.

What CDC is doing

CDC has been involved in studies over many years that have looked at how common neutralizing antibodies (a sign of prior infection) to H5N1 bird flu virus are among people with exposure to infected animals, as well as people with no such exposures. These studies can help inform ongoing public health risk assessments for H5N1 bird flu viruses. A review of these data supports the fact that human infections with H5N1 bird flu virus have been rare in the past, even among people with more extensive exposures. CDC is developing protocols for seroprevalence studies it hopes to conduct related to the H5N1 bird flu virus outbreak in dairy cattle.

What to know

• Seroprevalence studies are studies that test blood for the presence of to a pathogen of interest, such as H5N1 bird flu virus. The body's immune response to a pathogen, like H5N1 bird flu virus, leads to the production of antibodies that work to diminish, obstruct, or neutralize the infection. Neutralizing antibodies are antibodies that defend a cell from a pathogen by disrupting its ability to infect a cell. Detecting "neutralizing" antibodies specific to H5N1 bird flu viruses in blood could be evidence of prior infection with the virus.
• In an H5N1 bird flu virus antibody seroprevalence study, blood that tests positive for neutralizing antibodies to H5N1 bird flu virus is referred to as seropositive. The percentage of people in a study population who have neutralizing antibodies to a particular virus is called "seroprevalence."
• Data to date show that, although many people have been monitored after exposure to H5N1 bird flu virus-infected poultry, wild birds, and confirmed human patients globally, very few human infections have been detected.
• Seroprevalence data also show little to no evidence of prior H5N1 bird flu virus infections, even in populations exposed to infected poultry and wild birds without wearing any protective equipment, indicating that the virus has not spread well to or among people to date.
• Seroprevalence studies in people are included among the activities that CDC is planning related to the current H5N1 bird flu virus outbreak in dairy cows and other animals in the United States.
• The current assessment of the risk level to the general public is low. This is based on available epidemiologic and laboratory data to date.
• Although previous seroprevalence data are reassuring, because influenza viruses constantly change, continued surveillance and preparedness efforts are critical. CDC is monitoring for any changes that may change the agency's risk assessment.

Globally, Reported Human Infections with H5N1 Bird Flu Viruses Have Been Rare

CDC has been tracking H5N1 bird flu viruses globally for more than 26 years. While H5N1 bird flu viruses have been spreading widely for many years in wild birds and causing poultry outbreaks, most notably in Asia, the number of resulting human infections with these viruses has been relatively low. There have been fewer than a thousand sporadic, reported infections in people from 24 countries from 2003 to 2024. There is always concern that cases may be missed in people with minor symptoms or who experience other barriers to testing, but serologic studies to date offer supporting evidence and indicate that infections with these viruses to date have been rare, even among people with higher-risk exposures.

H5N1 Seroprevalence Studies

Seroprevalence studies are helpful because knowing if there have been prior infections with a virus can show if and how commonly the virus is infecting people. Information gathered from seroprevalence studies can help inform the process of iterative, ongoing risk assessments.

Studies that have tested the blood of people who work in poultry markets in Asia to look for H5N1 bird flu virus neutralizing antibodies (a sign of prior infection) have shown a low prevalence of infections. A 2020 systematic review and meta-analysis of more than 60 peer reviewed articles (from January 1, 1997-September 1, 2020) looked at H5N1 bird flu virus neutralizing antibody seroprevalence studies among people who had poultry exposures as well as people without specific exposures to poultry. Seroprevalence of H5N1 bird flu virus was higher among people with poultry exposures, compared with people who did not have exposure to poultry, but overall, neutralizing antibody levels were nonexistent or at very low frequencies among both groups of people.

The findings suggest that H5N1 bird flu viruses have not caused a large number of human infections, even in people exposed to virus-infected animals, and overall, these viruses have not been well adapted to spread to and among people. Importantly, studies also found that human seropositivity has been lower with more recent clades of H5N1 bird flu viruses circulating in wild birds and causing poultry outbreaks than it was with earlier H5N1 bird flu viruses. However, the systematic review and meta-analysis study reaffirmed that risk does increase with exposure, and people who have close, prolonged contact with infected animals, their byproducts, or environments may be at increased risk of H5N1 bird flu virus infection.

In the United States, a 2022 CDC study looked at the risk for symptomatic H5N1 bird flu virus infection in 4,000 people who had been exposed to H5N1 bird flu virus-infected poultry during February 7─September 3, 2022. Only one lab-confirmed human case of influenza H5N1 bird flu was detected. To assess whether asymptomatic or undetected cases had occurred, serologic testing was done among people with relevant exposures in two states. The serology testing did not show any evidence of people having neutralizing antibodies to A(H5N1) clade 2.3.4.4b viruses, the predominant virus circulating in birds and other animals in the United States. While the number of participants with serologic specimens was small, the information is still suggestive that human infections with these viruses, even among exposed people, are rare.

Seroprevalence Studies Moving Forward

In the context of the multistate outbreak of H5N1 bird flu virus in dairy cows with three human infections in the United States, many people are asking whether human cases are being missed. CDC hopes to conduct a number of seroprevalence studies to further inform the public health risk assessment for this virus in its present iteration. These studies would look at serology data from people who have been exposed to dairy cows infected with H5N1 bird flu virus to determine if there is evidence of neutralizing antibodies to H5N1 bird flu virus, indicative of prior human infections. These data would inform if any human detections have been missed.

Although seroprevalence data to date are reassuring, it is important for CDC to continually assess the public health risk of viruses that have pandemic potential, like H5N1 bird flu viruses. Viruses that have pandemic potential are of extra concern because of the impact they could have on public health if they were to gain the ability to spread easily from person to person and cause the next flu pandemic. While the three U.S. human cases of H5N1 bird flu had relatively mild illness, globally, H5N1 bird flu virus infections in people have ranged in severity from mild to deadly, with about a 50% fatality rate historically. Because influenza viruses constantly change, continued surveillance and preparedness efforts are critical, and CDC is monitoring for any changes that may change the agency's risk assessment.

CDC is beginning the process of conducting a pandemic risk assessment on the virus from the human infection in Texas (A/Texas/37/2024) using the Influenza Risk Assessment Tool (IRAT), which is a multi-step process that can take months to complete. The current assessment of the risk level to the general public, which is based on available epidemiologic and laboratory data, is low.

Recommended Prevention Measures

At this time, CDC believes that the overall risk to the general public posed by this virus remains low; however, people should take precautions.

• People should avoid exposures to sick or dead animals, including wild birds, poultry, other domesticated birds, and other wild or domesticated animals (including cows), if possible.
• People should also avoid exposures to animal poop, bedding (litter), unpasteurized ("raw") milk, or materials that have been touched by, or close to, birds or other animals with suspected or confirmed H5N1 bird flu virus, if possible.
• People who have job-related contact with infected or potentially infected birds or other animals should be aware of the risk of exposure to avian influenza viruses and should take proper precautions. People should wear appropriate and recommended personal protective equipment when exposed to an infected or potentially infected animal(s). CDC has recommendations for worker protection and use of personal protective equipment (PPE).
• High levels of H5N1 bird flu virus have been found in unpasteurized (raw) milk from infected cows. CDC and FDA recommend against the consumption of raw milk or raw milk products. The risk of human infection from drinking raw milk containing live H5N1 bird flu virus specifically is unknown, but it could be dangerous.