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US - CDC: Influenza Risk Assessment Tool (IRAT) - May 9, 2024

sharon sanders

Editor-in-Chief & President
Influenza Risk Assessment Tool (IRAT)

Public Health
May 9, 2024​


Purpose


The Influenza Risk Assessment Tool (IRAT) is an evaluation tool developed by CDC and external influenza experts that assesses the potential pandemic risk posed by influenza A viruses that currently circulate in animals but not in humans.

IRAT: Assessing Pandemic Risk


The IRAT assesses potential pandemic risk based on two questions: "emergence" and "public health impact."

These questions are listed as follows:
  1. Emergence asks the question: What is the risk that a virus not currently circulating in the human population has the potential for sustained human-to-human transmission?
  2. Public health impact asks the question: If the virus were to achieve sus­tained human-to-human transmission, what is the risk that a virus not currently circulating in the human population has the potential for significant impact on public health?
Emergence refers to the risk of a novel (i.e., new in humans) influenza virus acquiring the ability to spread easily and efficiently in people.

Public health impact refers to the potential severity of human disease caused by the virus (e.g., deaths and hospitalizations) as well as the burden on society (e.g., missed workdays, strain on hospital capacity and resources, and interruption of basic public services) if a novel influenza virus were to begin spreading efficiently and sustainably among people.


IRAT's 10 Risk Elements


The IRAT uses 10 risk elements to measure the potential pandemic risk associated with each of these questions. These 10 risk elements can be grouped into three overarching categories: "properties of the virus," "attributes of the population," and "ecology & epidemiology of the virus." Influenza subject matter experts evaluate novel influenza viruses based on each of these 10 risk elements.

Each of the 10 risk elements is then weighted statistically based on its significance to each of the two questions. A composite score for each virus is then calculated based on the given question. These composite scores provide a means to rank and compare influenza viruses to each other in terms of their potential pandemic risk for each of the two questions.

As we learn more about influenza A viruses, these 10 risk elements may change, other risk elements may be added, or some current risk elements may be dropped. The IRAT is designed to be flexible and responsive to current scientific advances.

IRAT's Key Objectives


The IRAT is intended to do the following:
  • Prioritize and maximize investments in pandemic preparedness by helping to determine which novel (new) influenza viruses to develop vaccines against and capitalizing on surveillance efforts and in-country capacity-building activities;
  • Identify key gaps in information and knowledge which can be the basis to prompt additional studies (for example, if information is not available for one of the 10 risk elements used by the IRAT additional studies could be done or resources allocated to provide the missing information);
  • Document in a transparent manner the data and scientific process used to inform decisions associated with pandemic preparedness;
  • Provide a flexible means to uniformly and regularly update the risk assessment of a novel influenza virus as new information becomes available;
  • Be an effective evaluation tool for public health and medical professionals;
  • Provide a means to weigh the 10 risk elements differently depending on whether the intent of the risk assessment is to:
  • measure the ability of an influenza virus to "emerge" as a pandemic capable virus (i.e., become capable of efficient human-to-human spread) or "impact" the human population if it did emerge.
IRAT's Limitations


The IRAT cannot predict the next pandemic and is not intended to do so. Additionally, the IRAT depends on subject matter experts to carefully analyze the 10 risk elements of the IRAT to determine pandemic risk and to rank the importance of the risk elements according to the specific risk question or situation.

The IRAT is not intended to provide a precise measurement of risk:
  • Many risk assessments generate a quantitative measure that describes the likelihood of exposure or disease risk. The IRAT focuses on the perceived pandemic potential of novel influenza viruses as estimated by subject matter experts using the IRAT risk elements and available data.
  • The IRAT depends on data that are often scarce and/or preliminary (for example, typically, when the IRAT is run, there are a small number of cases of human infection which may not provide a reliable estimate of public health impact).
IRAT's Overarching Categories


The IRAT consists of 10 risk elements grouped within three overarching categories. These categories and risk elements are described as follows:
  • The "Properties of the Virus" category contains four of the 10 risk elements, including:
    • Genomic analysis is a measure of the extent of genetic diversity or presence of known molecular signatures important for human infections and disease.
    • Receptor binding refers to the host preference (e.g., animal or human) of an influenza virus as well as the types of tissues and cells the virus is best suited to infecting (e.g., nose tissue and cells vs. deep lung tissue and cells). Some influenza viruses are better adapted to infecting humans than animals.
    • Transmission in animal models is a measure of the ability of an influenza virus to transmit efficiently in animals in laboratory studies. Some influenza viruses can transmit through the air via small infectious droplets expelled through coughs or sneezes. In contrast, other influenza viruses may only spread through direct contact with an infected host.
    • Antiviral treatment options refers to the predicted effectiveness of influenza antiviral medications, such as oseltamivir, zanamivir, baloxavir, and M2 blockers.
  • The "Attributes of the Population" category contains three of the 10 risk elements, including:
    • Population immunity refers to whether the human population has any existing immune protection against the novel influenza virus being evaluated. Susceptibility to infection and severity of illness associated with specific influenza viruses may depend on age, geographic area, or genetic factors.
    • Disease severity and pathogenesis measure the severity of illness caused by a particular influenza virus in people and/or animals.
    • Antigenic relatedness is a measure of how similar an influenza virus not circulating in humans is to seasonal influenza vaccines, pre-pandemic candidate vaccine viruses, and stockpiled pre-pandemic vaccines.
  • The "Ecology and Epidemiology" category contains the final risk elements, including:
    • Global distribution in animals measures how widespread an influenza virus is in animals, the rate of spread over time, and any management factors that may affect the distributi.
    • Infections in animals refers to what kinds of animals are impacted by the influenza virus and the likelihood of human contact with these animals. For example, are influenza infections occurring in wild birds or domestic birds?
    • Human infections refers to evidence and frequency of human infections with an influenza virus not currently capable of sustained human-to-human transmission. If evidence exists, under what circumstances do human infections occur? For example, how frequently and easily does transmission occur after direct and prolonged contact between humans and infected animals?
IRAT’s 10 Risk Elements

Risk Elements: Ranked and Weighed


Influenza experts generate numerical values (point score) to estimate the pandemic risk associated with each of the 10 risk elements. The point scores fall into three general classifications of risk: low risk, moderate risk and high risk:
  • Low risk is associated with a point score between 1.0 and 3.9;
  • Moderate risk is associated with a point score between 4.0-7.9; and,
  • High risk is associated with a point score between 8.0-10.0.
IRAT’s 10 Risk Elements: Weighing


Each of the 10 risk elements is weighted according to its importance to each of the two questions on "emergence" and "public health impact."

Potential Emergence Risk (Column 3 in Table)

The first question is: "What is the risk that a novel virus has the potential for sustained human-to-human transmission?" The risk elements may be ranked and weighted as follows (with the first risk element receiving the highest rank and weight score, and the last risk element receiving the lowest rank and weight score).
  • Human infections
  • Transmission in animal models
  • Receptor binding
  • Population immunity
  • Infections in animals
  • Genomic analysis
  • Antigenic relatedness
  • Global distribution of animals
  • Disease severity and pathogenesis
  • Antiviral treatment options
Potential Impact Risk (Column 4 in Table)

The second question is: "If the virus were to achieve sustained human-to-human transmission, what is the risk that a novel virus has the potential for significant impact on public health?" The same risk elements could be ranked and weighted as follows (with the first risk element receiving the highest rank and weight score, and the last risk element receiving the lowest rank and weight score).
  • Disease severity and pathogenesis
  • Population immunity
  • Human infections
  • Antiviral treatment options
  • Antigenic relatedness
  • Receptor binding
  • Genomic analysis
  • Transmission in animal models
  • Global distribution in animals
  • Infections in animals
Acceptable Score Ranges

Mean-High and Mean-Low


Since the IRAT is qualitative in nature, its scores involve some degree of subjectivity. Subject matter experts provide a range of “acceptable” scores for each risk element by identifying a lower and upper bound they would consider acceptable from other experts scoring the same element. The mean of the lowest acceptable bound and the mean of the highest acceptable bound from each risk element are used in the weighted “emergence” or “public health impact” calculations to create the “mean-high” and “mean-low” acceptable score ranges.

Updating IRAT


The IRAT may be updated when new zoonotic or novel influenza viruses emerge or undergo a change in characteristics that prompts the need for a new assessment.

IRAT Virus Summaries


CDC has prepared a summary of Influenza Risk Assessment Tool (IRAT) results.


https://www.cdc.gov/pandemic-flu/php/national-strategy/influenza-risk-assessment-tool.html
 
Results of Influenza Risk Assessment Tool

Public Health
May 2, 2025​


At a glance
  • The Influenza Risk Assessment Tool (IRAT) is a CDC evaluation tool developed with assistance from global animal and human health influenza experts.
  • The IRAT is used to assess the potential pandemic risk of influenza A viruses that are not currently circulating in people.
  • This latest IRAT assessed two recent clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024.
  • These viruses scored in the "moderate risk" category for potential emergence and public health impact, similar to previous assessments of earlier clade 2.3.4.4b avian influenza A(H5N1) viruses. These results validate the proactive, coordinated U.S. government response.
  • The IRAT does not assess the immediate risk to the public's health, which is unchanged and remains low, and it does not predict future pandemics.
Purpose


The IRAT uses expert opinion to evaluate the potential of a representative novel influenza A virus to gain the ability for person-to-person spread and the resulting potential public health impact if that were to happen, and it allows for comparison to other viruses evaluated in past IRAT reports. The IRAT does not assess the immediate risk to the public's health, and it does not predict future pandemics. The immediate risk to the public's health from clade 2.3.4.4b avian influenza A(H5N1) viruses is unchanged and is currently considered to be low. The current H5N1 bird flu situation continues to be mostly an animal health issue. Human infections with avian influenza A(H5N1) viruses are rare, and these viruses still are not well-adapted to spreading among people, as they do not currently have the ability to easily infect the human upper respiratory tract. Of the 70 cases in the United States from 2024-2025, 41 were associated with exposure to influenza A(H5N1)-infected cattle and 24 were associated with exposure to influenza A(H5N1)-infected poultry/birds. In addition, there were two cases with backyard poultry exposure and three cases with unknown exposure. Globally, most past human infections with avian influenza A(H5N1) viruses have occurred following close, unprotected contact with sick or dead birds.

This report summarizes the findings of an IRAT conducted on two viruses that caused recent human illnesses: A/California/147/2024 and A/Washington/239/2024. The resulting score places both of these viruses, representative of two main groups of avian influenza A(H5N1) viruses currently circulating among animals in the United States, in the category of "moderate risk" for potential future emergence and public health impact. This is similar to previous assessments of earlier avian influenza A(H5N1) viruses. The scores for this IRAT were submitted on March 14, 2025.

During a public health response, the IRAT can be used to assess the appropriateness of the ongoing response efforts and whether additional actions are warranted based on the risk score. The results of this IRAT validate the proactive, coordinated U.S. government response. Assessing risk is an iterative process with new information being assimilated regularly and response activities adjusted as indicated.

Key findings


On May 2, 2025, CDC published a new IRAT assessment for two clade 2.3.4.4b avian influenza A(H5N1) viruses: A/California/147/2024 and A/Washington/239/2024. A/California/147/2024 is a B3.13 genotype virus, like the ones currently circulating in dairy cows in the United States and causing sporadic human infections, mostly among people who had exposure to H5N1 virus-infected or presumed infected dairy cattle. A/Washington/239/2024 is a D1.1 genotype virus, like those that are most commonly circulating in wild/migratory birds and also causing poultry outbreaks and sporadic human illnesses, mostly among people who had exposure to poultry confirmed to have influenza A(H5N1) virus infection. The genes of this virus are more closely related to what has been circulating most commonly in U.S. wild birds and poultry.

Previously, CDC assessed three other clade 2.3.4.4b avian influenza A(H5N1) viruses, including A/American wigeon/South Carolina/AH0195145/2021, A/mink/Spain/3691-8_22VIR10586-10/2022, and A/Texas/37/2024. All three previously assessed viruses had overall estimated IRAT scores in the moderate risk category range of 4.0 to 7.9.

This updated assessment includes new information, including information from additional human cases reported in the United States. This updated assessment indicates that these two viruses (A/California/147/2024 and A/Washington/239/2024) scored slightly lower in some risk elements and slightly higher in others compared with the previously assessed H5N1 clade 2.3.4.4b viruses. However, the mean-high and mean-low acceptable score ranges for these viruses overlap, indicating that these viruses remain similar, and their overall risk scores remain "moderate."
  • The average risk scores for the potential emergence of the A/California/147/2024 and A/Washington/239/2024 viruses were 5.59 and 5.21, respectively, placing them in the mid-low range of the moderate risk category.
  • The average risk scores for these two viruses to potentially impact public health was 5.91 and 6.00, respectively, placing them in the mid-range of the moderate risk category.
These scores reflect a decrease of at least 0.20 in the potential emergence question and a decrease of at least 0.09 in the potential public health impact question compared with the previous A/Texas/37/2024 virus evaluation from last year, but both questions on emergence and public health impact still fall into the moderate risk category.

Some variation was seen among subject matter expert (SME) point estimate scores across the risk elements, including Human Infections and Infections in Animals, where the scores ranged from moderate to high risk for the A/California/147/2024 virus, and Disease Severity and Pathogenesis, Global Distribution of Animal Influenza Viruses, and Human Infections for the A/Washington/239/2024 virus. This indicates some uncertainty in interpretation and confidence of the available data.

Sensitivity analyses using the lowest and highest scores for these four risk elements resulted in adjusted ranges for the overall emergence risk and the potential impact risk that continued to place this virus in the mid-range of the moderate risk category. This indicates that the categorization of HPAI A(H5N1) clade 2.3.4.4b virus, including A/California/147/2024 and A/Washington/239/2024, as moderate risk was unchanged by the range of scores within the risk elements exhibiting variation.

The full report is available at Virus Descriptions and Report Summaries.

Background


Input on IRAT assessments is provided by a diverse group of U.S. government animal and human health influenza experts. More information about the IRAT, including a description of its methodology and definitions for its risk elements and categories, is available at Influenza Risk Assessment Tool (IRAT). The IRAT is updated when new zoonotic or novel influenza A viruses with pandemic potential emerge or undergo a change in characteristics that prompts the need for a new assessment.


Summary of U.S. Human Cases of H5 Bird Flu


In the United States since April 2024, 70 human illnesses with H5 bird flu have been reported in 13 states. One additional human case of H5N1 bird flu was reported in the United States in April 2022 in a farm worker who experienced fatigue without any other symptoms and while depopulating poultry at a poultry farm with confirmed avian influenza A(H5N1) virus.


Summary of U.S. human cases associated with dairy cattle exposure


The first human case in the United States associated with the outbreaks of A(H5N1) virus among dairy cattle was reported on April 1, 2024, by the State of Texas. As of April 2024, 41 human cases of H5 bird flu have been associated with the ongoing multi-state outbreak of A(H5N1) in dairy cattle, with 36 cases occurring in California, two cases in Michigan, and one case each reported in Colorado, Nevada and Texas. All infections occurred in dairy workers who had direct exposure to cattle presumed to be infected with A(H5N1) virus. Infections associated with U.S. dairy cattle to date have involved mild respiratory symptoms or conjunctivitis. No patients have been hospitalized.


Summary of U.S. human cases associated with poultry or backyard flock exposure


Twenty-four human cases of H5 bird flu have been detected in farm workers who were involved in the depopulation of poultry at a poultry facility experiencing an outbreak of HPAI A(H5N1) virus, and two cases involved exposures to backyard flocks in Louisiana and Wyoming. Eleven of the 24 cases in farm workers were reported in Washington state, nine in Colorado, and one each in Iowa, Ohio, Oregon, and Wyoming. Most of these workers who tested positive reported mild illness, such as redness/watery eyes and respiratory symptoms. However, one case in Ohio was severe and required hospitalization; the patient subsequently recovered. In addition, the two cases exposed to backyard birds were severe, required hospitalization, and one died.


Summary of U.S. human cases with no known animal exposure


The exposure source is unknown for three cases, two cases in children in California and one adult case in Missouri.

Influenza A viruses assessed

View LargerDownload
2025-irat-virus-emergence.png
This dot graph plots the average weighted risk scores for “public health impact” and “emergence” for viruses subjectively assessed by the IRAT’s panel of expert reviewers.
AA(H1N1) [A/swine/Shandong/1207/2016]7.56.9
BA(H7N9) [A/Hong Kong/125/2017]6.57.5
CA(H5N1) Clade 2.3.4.4b [A/Texas/37/2024]5.86.1
DA(H5N1) Clade 2.3.4.4b [A/California/147/2024]5.66
EA(H5N1) Clade 2.3.4.4b [A/Washington/239/2024]5.26
FA(H5N1) Clade 2.3.4.4b [A/mink/Spain/3691-8_22VIR10586-10/2022]5.16.2
GA(H5N1) Clade 2.3.4.4b [A/American wigeon/South Carolina/AH0195145/2021]4.45.1
HA(H7N9) [A/chicken/Tennessee/17-007431-3/2017]3.13.5
IA(H7N9) [A/chicken/Tennessee/17-007147-2/2017]2.83.5
JA(H1N1) [A/duck/New York/1996]2.32.4
Footnote: In this dot graph, the average score estimates for the potential emergence and public health impact risk elements for the HPAI A(H5N1) clade 2.3.4.4b virus A/California/147/2024 (shown as D) and A/Washington/239/2024 (shown as E) viruses were plotted along with the scores of the previous A(H5N1) clade 2.3.4.4b viruses scored using the IRAT (Figure). The estimates for the current A(H5N1) clade 2.3.4.4b viruses were in the mid-moderate range for both risk of potential emergence and risk of potential public health impact. Additionally, the range of the mean low acceptable and the mean high acceptable scores of A/California/147/2024 and A/Washington/239/2024 viruses overlap with the previously scored A(H5N1) clade 2.3.4.4b viruses (Figure). More information about how the IRAT calculates risk scores is available at Influenza Risk Assessment Tool (IRAT).

Note: The letters in the 'dot' column of this table correspond to those in the dot graph above.

IRAT data table


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A(H1N1) [A/swine/Shandong/1207/2016]20-Jul7.56.96.338.655.428.09
A(H3N2) variant [A/Ohio/13/2017]19-Jul6.65.85.017.594.097.26
A(H7N9) [A/Hong Kong/125/2017]17-May6.57.55.657.516.748.5
A(H7N9) [A/Shanghai/02/2013]16-Apr6.47.25.527.436.418.32
A(H9N2) Y280 lineage [A/Anhui-Lujiang/13/2018]19-Jul6.25.94.767.574.37.3
A(H3N2) variant [A/Indiana/08/2011]12-Dec64.5N/AN/AN/AN/A
A(H1N2) variant [A/California/62/2018]19-Jul5.85.74.227.163.87.09
A(H5N1) Clade 2.3.4.4b [A/Texas/37/2024]24-Jun5.86.14.377.024.677.3
A(H5N1) Clade 2.3.4.4b [A/California/147/2024]25-Mar5.664.096.784.597.22
A(H9N2) G1 lineage [A/Bangladesh/0994/2011]14-Feb5.65.44.496.744.416.65
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Virus comparison by risk element score

H5N1 Clade 2.3.4.4b Virus Comparison by Risk Element Score

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02.04.06.08.010.0Risk ScoreAntigenicRelatednessAntiviralTreatmentOptions DiseaseSeverityandPathogenesisGenomicAnalysisGloba lDistributioninAnimalsHumanInfectionsInfectionsinA nimalsPopulationImmunityReceptorBindingTransmissio ninAnimalModelsRisk Element Skip Data Table
Data Table Download Data (CSV)
Skipped data table.

Footnote: This bar graph shows how the March 14, 2025, IRAT assessments of A/California/147/2024 and A/Washington/239/2024 viruses compares with the June 2024 assessment of A(H5N1) Clade 2.3.4.4b [A/Texas/37/2024] virus and the April 2023 and March 2022 assessments for the A(H5N1) Clade 2.3.4.4b [A/mink/Spain/3691-8_22VIR10586-10/2022] and A(H5N1) Clade 2.3.4.4b [A/American wigeon/South Carolina/AH0195145/2021] viruses, across each of the IRAT's 10 risk elements. These 10 risk elements are weighted differently when scoring a virus' risk of emergence versus its risk of public health impact. Definitions for these risk elements and additional information on how these risk elements are weighted when determining viruses' risk of emergence versus risk of public health are available at Influenza Risk Assessment Tool (IRAT).

https://www.cdc.gov/pandemic-flu/php/monitoring/irat-virus-summaries.html

 
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