03 influenza Shimabukuro 508

CDC ACIP — Vaccine Advisory Committee

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Highly Pathogenic 
Avian Influenza A 
(H5N1)
Tom Shimabukuro, MD, MPH, MBA
 
Influenza Division
National Center for Immunization and Respiratory 
Diseases (NCIRD)
Centers for Disease Control and Prevention (CDC)
October 23, 2024
HPAI A(H5N1)/ HPAI A(H5)  Human Cases Since 1997
Past Reported Global Human Cases with Highly Pathogenic Avian Influenza A(H5N1) (HPAI H5N1) by Country, 1997 -2024 | Bird Flu | C DC (Thru Aug 7, 2024; may include  A(H5)+, presumed H5N1 cases) 2

•Historically, human infections have been 
the result of:
▪Poultry exposures 
oDirect/close contact with sick or 
dead poultry
oVisiting a live poultry market
▪Exposure to other infected animals
oDirect contact or close exposure 
(swans, dairy cows)
▪Limited, non -sustained human -to-
human transmission has occurred 
globally in the past (not in the 
United States)Historical Human Exposures to HPAI A(H5N1) Viruses
3
CDC’s Priorities 
•Supporting and engaging  public 
health and agricultural partners
•Protecting human health and 
safety 
•Understanding risk to people 
from HPAI A(H5N1) viruses
•Assessing HPAI A(H5N1) viruses 
for genetic changes
Avian Influenza Social Media Toolkit | Bird Flu | CDC
4

HPAI A(H5N1) Situation Update – Dairy Herds
•As of October 18, 2024, USDA 
has confirmed HPAI A(H5N1) 
in U.S. dairy herds in 324 
farms across 14 states
▪Dairy cow illness was observed in 
early 2024
▪Significant decrease in milk 
production and quality
▪March 25, 2024 : USDA reported 
HPAI A(H5N1) confirmed in cows 
from Texas and Kansas
Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock | Animal and Plant Health Inspection Service (usda.gov)  5

HPAI A(H5) Human Cases, United States, During 2024 
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H5 Bird Flu: Current Situation | Bird Flu | CDC  (all cases ≥18 years old, data through Oct 18, 2024)•Cases with dairy cattle and poultry exposures 
have been clinically mild
▪Mainly eye symptoms (conjunctivitis, eye 
discharge)
▪Some cases reported mild respiratory and 
systemic symptoms (e.g., subjective fever)
•The Missouri case had multiple underlying health 
conditions and was hospitalized with 
gastrointestinal symptoms, chest pain, and other 
symptoms not typical of a respiratory illness and 
tested positive for influenza A
▪Illness was not severe, patient treated with 
oseltamivir and recovered
▪Specimen was identified and confirmed as 
HPAI A(H5N1) through regular surveillance 
▪Serology results are pending on the case, a 
symptomatic household contact of the case, 
and several exposed healthcare workers 
who experienced mild respiratory illness
Influenza A(H5) Human Cases –Virus Sequences to Date
•Sequences maintain primarily avian genetic characteristics and lack 
changes that would make the virus better adapted to infect or spread 
among humans
•Diagnostics :No impact to the current CDC influenza diagnostic 
assay's ability to detect A(H5N1) viruses
•Treatments :No known markers of resistance to FDA approved antiviral 
drugs for influenza 
•Candidate Vaccine Viruses (CVVs)
▪Hemagglutinins of human influenza viruses remain antigenically related to two 
available CVVs
How CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation | Bird Flu | CDC7
•All people with direct or close exposure to animals infected 
with influenza A(H5N1) should be monitored for illness 
during exposure and for 10 days after their last exposure
•Signs/symptoms may include: 
▪feeling feverish, cough, sore throat, runny or stuffy nose, muscle or 
body aches, headaches , fatigue , eye redness (or conjunctivitis) , 
shortness of breath or difficulty breathing
▪less commonly, diarrhea, nausea, vomiting, or seizures
•If signs/symptoms develop, seek medical evaluation for 
possible influenza testing and antiviral treatment
•Symptomatic persons should isolate away from others during 
this evaluation
•State and local h ealth de partments are monitoring workers on 
impacted farms and can facilitate testing and treatmentSymptom Monitoring Recommendations 
https://my.clevelandclinic.org/health/diseases/22401 -bird-flu
8Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public He alth 
Investigations | Bird Flu | CDC ; Interim Guidance on Specimen Collection and Testing for Patients with Suspected Infection with Novel Influenza 
A Viruses Associated with Severe Disease or with the Potential to Cause Severe Disease in Humans | Bird Flu | CDC
•CDC is continuing to 
support state and local 
health departments 
monitoring exposed 
people during and for 10 
days after last exposureOngoing Human Monitoring
H5 Bird Flu: Current Situation | Bird Flu | CDC
How CDC is monitoring influenza data among people to better understand 
the current avian influenza A (H5N1) situation | Bird Flu | CDC
(Through Oct 18, 2024)
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Since Feb 2024, public health laboratory monitoring includes testing of over 54,360 specimens using a protocol that 
would have detected influenza A(H5) or other novel influenza viruses, 1 person has tested positive (the Missouri case)Surveillance, Human Monitoring, and Testing
How CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation | Bird Flu | CDC , Weekly U.S. Influenza Surveillance Report | CDC10
No indicators of unusual influenza 
activity in people, including avian 
influenza A(H5N1)
Findings from a Michigan Seroprevalence Study
•In June 2024, Michigan Department of Health collected blood 
samples from 35 dairy workers
▪had varying roles, but most worked with infected cows
▪less than half reported using masks or goggles
•Samples were tested for antibodies against influenza A(H5N1) 
virus and a seasonal influenza virus
•None of the participants showed neutralizing antibodies specific 
to avian influenza A(H5N1) virus, although many showed 
antibody responses to seasonal influenza virus
•This suggests that these people were not previously infected 
with influenza A (H5N1) despite high risk of exposure
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Ferret Studies
•Ferret model permits study of influenza disease severity and transmissibility 
at the same time
•Ferrets present with many clinical signs of infection shared by humans
▪But not conjunctivitis
•Limitations of ferret model
▪Ferrets  in sustained contact 24/7
▪Inoculation doses used in these studies may not be representative of natural exposure 
in humans
▪Ferrets used in most studies have no preexisting antibodies to influenza, unlike most 
humans who have had disease or vaccinations
▪General limitations of animal models
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Pathogenesis and Transmission of Human Influenza 
A(H5N1) Viruses in Ferrets
13*Pulit -Penaloza  et al, manuscript in press; †Brock et al, manuscript in preparationInfluenza A(H5N1) VirusMean  Max
Weight Loss
(inoculated ferrets)Lethality
(inoculated ferrets)Direct Contact
Transmission
(ferrets co -housed)Resp Droplet
Transmission
(refer to image)
A/Texas/37/2024(H5N1)
(1st human case in 2024)* 13% 9/9 (100%) 3/3 (100%) 4/6 (66%)
A/Michigan/90/2024 (H5N1)
(2ndhuman case in 2024)†9.1% 0/6 (0%) 3/3 (100%) 2/3 (66%)
Respiratory droplet (airborne) 
transmission model
Inoculated ferretNaïve ferret
Direct contact 
transmission model
Ferret Studies Summary
•Severity
▪The Michigan human A(H5N1) virus caused less severe disease  in ferrets than the Texas 
human A(H5N1) virus
▪Less mean maximum weight loss, 9.1% vs. 13%
▪Lower lethality, 0/6 (0%) vs. 9/9 (100%)
•Transmission
▪The Michigan human A(H5N1) virus still transmits with some capacity by the respiratory 
droplet route, similar to  what was observed with Texas human A(H5N1) virus
•These findings are important because the Michigan human A(H5N1) virus 
better represents currently circulating viruses compared to the Texas human 
A(H5N1) virus
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CDC Influenza Risk Assessment Tool (IRAT)
•Evaluative tool for prioritizing 
resources for pandemic 
preparedness
•Viruses scored using 10 risk 
elements by U.S. government 
subject matter experts for 
emergence and public health 
impact
•Emergence  is the risk of a novel 
influenza virus acquiring the 
ability to spread easily and 
efficiently in people
•Public health impact is the 
potential severity of human 
disease caused by the virus, the 
burden on society if a novel 
influenza virus were to begin 
spreading efficiently and 
sustainably among people1.Genomic variation 
2.Receptor binding
3.Transmission in Laboratory animals
4.Antivirals and Treatment Options
5.Existing Population Immunity
6.Disease Severity and Pathogenesis
7.Antigenic Relationship to Vaccine Candidates
8.Global Geographic Distribution
9.Infection in Animals, Human Risk of Infection
10.Human Infections and Transmission
Virus
Population
Ecology
Influenza Risk Assessment Tool (IRAT) | Pandemic Flu | CDC 15
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10Impact
EmergenceIRAT Virus Emergence and Impact – Comparison of Risk Scores
Influenza Risk Assessment Tool (IRAT) | Pandemic Influenza (Flu) | CDC• X: H5N1 clade 2.3.4.4b [A/Texas/37/2024ª] (X)
Emergence = 5.8, Impact = 6.1
• A: Highest emergence score Eurasian Avian/swine H1N1 in China
Emergence = 7.5, Impact = 6.9
• C: Highest Impact score avian H7N9 in China 
 Emergence = 6.5, Impact = 7.5Data 
labelInfluenza VirusEmergence 
ScoreImpact 
Score
A A(H1N1) [A/swine/Shandong/1207/2016] 7.5 6.9
B A(H3N2) variant [A/Ohio/13/2017] 6.6 5.8
C A(H7N9) [A/Hong Kong/125/2017] 6.5 7.5
E A(H9N2) Y280 lineage [A/Anhui -Lujiang/13/2018] 6.2 5.9
F A(H3N2) variant [A/Indiana/08/2011] 6.0 4.5
X A(H5N1) clade 2.3.4.4b [A/Texas/37/2024A] 5.8 6.1
G A(H1N2) variant [A/California/62/2018] 5.8 5.7
I A(H5N6) clade 2.3.4.4b [A/Sichuan/06681/2021] 5.3 6.3
J A(H5N1) Clade 1 [A/Vietnam/1203/2004] 5.2 6.6
KA(H5N1) Clade 2.3.4.4b [A/mink/Spain/3691 -
8_22VIR10586 -10/2022]5.1 6.2
L A(H5N6) [A/Yunnan/14564/2015] –like 5.0 6.6
N A(H5N8) clade 2.3.4.4b [A/Astrakhan/3212/2020] 4.6 5.2
OA(H5N1) clade 2.3.4.4b [A/American  
wigeon/South Carolina/AH0195145/2021]4.4 5.1
Q A(H5N8) [A/gyrfalcon/Washington/41088/2014] 4.2 4.6
U A(H7N8) [A/turkey/Indiana/1573 -2/2016] 3.4 3.9
VA(H7N9) [A/chicken/Tennessee/17 -007431 -
3/2017]3.1 3.5X: Texas H5N1 2024
K: mink/Spain H5N1 2022
O: wigeon/SC H5N1 2021
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IRAT Summary 
•The IRAT is an evaluative tool used by public health partners  for prioritizing 
resources for influenza pandemic preparedness
•ItisNOT intended to predict a pandemic and is NOT to be used to assess the 
overall population risk nor individual risk
•Using A(H5N1) clade 2.3.4.4b [A/Texas/37/2024(H5N1)] as the prototype virus, the 
score remains in the "moderate" potential pandemic influenza risk category
•The mean -high and mean -low acceptable score ranges for all the clade 2.3.4.4b 
viruses overlap, indicating that these viruses remain similar, and their overall risk 
scores remain "moderate"
•Based on available data, CDC’s current assessment is that the risk to the general 
public from avian influenza A(H5N1) virus remains low
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Public Health Risk
•Overall risk to the public for HPAI A(H5N1) 
remains low
•Greater risk for people with close, 
prolonged, or unprotected exposures to 
infected animals, or to environments 
contaminated by infected animals
•Exposed individuals should monitor for 
symptoms after first exposure and for 10 
days after last exposure
Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim 
Recommendations for Prevention, Monitoring, and Public Health 
Investigations | Avian Influenza (Flu) (cdc.gov)
Avian Influenza Social Media Toolkit | Bird Flu | CDC
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Avian Influenza Social Media Toolkit | Bird Flu | CDC
Avian Influenza Social Media Toolkit | Bird Flu | CDC
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Resources from CDC
Situation Updates
CDC A(H5N1) Bird Flu Response Update | Avian 
Influenza (Flu)
Surveillance Updates
How CDC is monitoring influenza data among people to 
better understand the current avian influenza A (H5N1) 
situation | Avian Influenza (Flu)
Technical Report
Technical Report: Highly Pathogenic Avian Influenza 
A(H5N1) Viruses | Avian Influenza (Flu) (cdc.gov)
Updated Recommendations
Highly Pathogenic Avian Influenza A(H5N1) Virus in 
Animals: Interim Recommendations for Prevention, 
Monitoring, and Public Health Investigations 
Recommendations for Worker Protection and Use of 
Personal Protective Equipment (PPE) to Reduce 
Exposure to Novel Influenza A Viruses Associated with 
Severe Disease in Humans
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Acknowledgments
CDC Influenza Division
•Virology, Surveillance, and Diagnosis Branch
•Epidemiology and Prevention Branch
•Immunology and Pathogenesis Branch
•Global Influenza Branch
•Office of the Director
CDC 2024 Influenza A(H5N1) Response
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Thank you