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A summary of presentations from the weekly Summit partner webinars

December 5, 2024 – The latest Summit Summary

Human Avian Influenza A H5N1 Cases in California – Kathleen Harriman, PhD, MPH, RN Epidemiology and Surveillance Lead for the H5N1 Response California Department of Public Health

Kathleen Harriman, PhD, MPH, RN gave an update about influenza A H5N1 cases in California; Tom Shimabukuro, MD, MPH, MBA gave an update about the highly pathogenic avian influenza A (H5N1); and Kimberly Armstrong, PhD, MT (ASCP) gave an update on vaccines and current strategies against H5N1.

Human Avian Influenza A H5N1 Cases in California – Kathleen Harriman, PhD, MPH, RN
The following is a review of influenza A H5N1 progression and cases in California.

H5N1 Detections in Dairy Cows in California
California has >1,000 dairy farms with >1.7M cows, which fall under the purview of the California Department of Food and Agriculture (CDFA).

  • The first three California dairy farms with infected cows were identified August 30, 2024.
  • As of December 2, 2024, H5N1 had been confirmed in dairy cows in 475 dairies in central California; in some affected counties, as many as 90% of herds have been affected.
    • There have been 30 infected commercial poultry flocks and 5 infected backyard flocks.

Management of Affected Herds (under the CDFA)

  • Symptomatic cows are placed in the hospital pen and its milk is excluded from the commercial milk supply.
  • If the farm veterinarian suspects influenza, the CDFA is contacted for H5 testing authorization. For positive cases…
    • After all sick cows have recovered, the bulk milk tank is tested weekly.
    • After 3 consecutive negative tests, herds are released from quarantine; CDFA testing continues and re-quarantine is possible.

U.S. Human Cases of Avian Influenza A(H5N1)
There have been 50 confirmed human case detections in the United States in 2024.

  • 21 cases were following poultry exposure; 35 were following exposure to infected dairy cows (of those, 31 were in California, 2 in Michigan, 1 in Texas, and 1 in Colorado); 2 cases had no known exposure to animals.
  • All the human cases have resulted in mild illness, many were limited to conjunctivitis but others presented with fevers and other mild symptoms.
    • One teenager in Canada has very severe illness and has been hospitalized for weeks. This teenager’s clade and genotype has been seen in poultry but differs from the genotype that has been in dairy cattle and in human cases in California.
  • To date, there has been no evidence of person-to-person spread in the United States.
  • Current risk to the general public is low. The priority focus is on dairy and poultry workers, including recommendations for seasonal influenza vaccine.

H5N1 Infections in California Dairy Workers
There are more than 17,500 dairy workers in California. The first two human cases of H5N1 in California were confirmed by CDC on October 3, 2024.

  • Personal protective equipment has been sent to farm workers, including respirators, gloves, goggles, face shields, and is typically available. However, there are barriers to its use: it’s hot, uncomfortable, googles can fog up, etc.
  • Workers on farms with infected cows are monitored for symptoms at the farm level.
  • Cases are presumptively confirmed at California public health labs and then samples are sent to CDC for confirmation. Commercial H5 testing is also available.

H5N1 Infections in California Dairy Workers (no confirmed poultry cases)
So far, there have been 31 confirmed cases and 1 probable case of H5N1 in California dairy workers.

  • All cases have been male, aged 19 to 57 years.
  • All have had mild illness; none have been hospitalized.
  • All 32 cases reported eye infection/redness; 10 reported fever, 9 reported muscle aches, and some had other mild symptoms.
    • Of the 24 people with confirmed cases and with job information, 19 were milkers and 3 took care of sick cows.
    • Presumed exposure was raw milk in eyes, by splashes or touching eyes with contaminated hands.

PPE used:

  • Of the 29 cases with PPE information, 25 reported using PPE, 4 reported not using PPE.
  • Of the 20 cases with information on eye protection, 18 reported using eye protection; of the 10 that reported the type of eye protection, they used goggles (1 also reported use of a face shield).

Test results:

  • 31 of 32 cases had positive conjunctival swabs.
  • 10 of 30 had positive nasal/oral pharyngeal (OP) swabs.
  • 4 of 32 had positive nasopharyngeal swabs.

How the virus might spread in dairy farms

  • Raw milk splashing into eyes, nose, or mouth
  • Touching eyes or mouth with contaminated hands
  • Inhaling tiny droplets of milk
  • Handling sick or dead barn cats, mice, or other infected animals
  • Drinking raw milk/eating raw milk products

CDPH Recommended PPE for Dairy Workers

  • Wash hands often/do not touch eyes
  • Use PPE when in contact with or around infected dairy cows
    • Eye protection
    • N95 or higher-level NIOSH-approved respirator
    • Gloves
    • Coveralls, aprons, head coverings, boots/shoe covers

Pediatric H5N1 Influenza Case
An Alameda County child with mild respiratory symptoms tested positive for influenza A(H5) on November 12, 2024 and the case was confirmed by CDC on November 21, 2024.

  • Partial sequencing revealed clade 2.3.4.4b, which is the clade in North American birds and dairy cows.
  • The child had no known exposure to infected animals.
  • The child was treated with oseltamivir and recovered.

Family members also had mild respiratory symptoms and tested negative for influenza A 4 days after the initial test in the child.

  • Family members received oseltamivir Post-Exposure Prophylaxis (PEP).
  • Child and 2 family members tested positive for rhinovirus and adenovirus.

Child attended daycare while ill.

  • Attendees and staff were offered oseltamivir PEP.
  • Contacts were monitored x 10 days and tested if symptomatic.
    • All tests were negative for influenza A.

CDPH Home Isolation Recommendations for H5N1 Cases

  • Suspect cases should stay home until H5N1 is ruled out.
  • Probable and confirmed cases should isolate at home until:
    • Eye infection has cleared up;
    • Fever has been gone for 24 hours without fever-reducing medication;
    • Other symptoms are mild and improving.
  • Oseltamivir recommended for all cases; oseltamivir PEP for household members.

CDPH Modified Work Isolation Recommendations
These recommendations may encourage more symptomatic people to come forward, as a positive test does not necessarily mean missed work/pay.

  • Suspect, probable, and confirmed cases may work if they are well enough to work and if they and their coworkers:
    • Wear recommended PPE;
    • Wash hands frequently with soap and water or use 60% alcohol-based hand sanitizer; and
    • Wear facemasks while together where PPE is typically not worn (e.g., breakrooms, transportation).

Challenges
Reporting and testing for symptoms

  • Symptomatic workers may not come forward
  • Employers may not report cases to the local health department
  • Issues with insurance or access to healthcare may interfere with referrals to the emergency department or urgent care

Providing oseltamivir for cases and household contacts

  • Medication may not be prescribed at time of testing and there may be insurance issues
  • Difficulty getting oseltamivir suspension for children
  • Little information about the H5N1 infectious period or about human-to-human spread

Testing of Suspect H5N1 Human Cases
Symptomatic people with possible exposure to infected animals or humans should have specimens tested by a public health laboratory with H5 subtyping capability.

  • The state public health laboratory should be notified about testing done by a local health department.
  • At least one commercial laboratory can now perform H5 subtyping on influenza A positive specimens; CDPH recommends this testing for low suspicion cases.
  • Commercial or clinical laboratory PCR tests for influenza A can be used to rule out influenza A (and therefore H5N1).

Key Messages for Clinicians

  • Consider influenza A (H5N1) infection in persons with acute respiratory symptoms and/or conjunctivitis; ask about exposure to animals.
  • Immediately report any suspected H5N1 infections to state and local health departments.
  • Testing of persons highly suspected to have H5N1 influenza infection should be done at public health laboratories with H5N1 testing capability.
  • Empiric influenza antiviral treatment is recommended for patients with suspected or confirmed H5N1 infection.
  • Follow standard contact and airborne precautions when caring for patients suspected of having H5N1 infection.

Resources for healthcare professionals were provided.

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Highly Pathogenic Avian Influenza A (H5N1) – Tom Shimabukuro, MD, MPH, MBA Deputy Director, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC)

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Highly Pathogenic Avian Influenza A (H5N1) – Tom Shimabukuro, MD, MPH, MBA
The uptick in highly pathogenic avian influenza (HPAI) A(H5N1) human cases in 2024 has largely been driven by cases in the United States associated with the outbreak in dairy cows and poultry.

  • Historically, human infections have been the result of poultry exposure.
  • Limited non-sustained human-to-human transmission has been reported globally, but not in the United States.

HPAI A(H5N1) Situation Update – Dairy Herds
USDA has confirmed HPAI A(H5N1) in U.S. dairy herds in 689 farms across 15 states; the USDA first reported HPAI A(H5N1) confirmed cases in cows on March 25, 2024, with the first signs being a significant decrease in milk production and quality.

  • As of December 2, 2024, there were 57 total human cases: 34 associated with dairy cow exposures, 21 with poultry exposures, and 2 with unknown exposures.
    • In August 2024, in Missouri, HPAI A(H5N1) was detected in an adult patient with multiple underlying health conditions: the illness was not severe; the patient was treated with oseltamivir and recovered; it was unclear whether it was the H5 infection that caused the patient’s symptoms.
    • In November 2024, in Canada, a teenager was hospitalized and subsequently diagnosed with H5N1 infection. The patient became critically ill during the hospitalization.
      • The Public Health Agency of Canada confirmed the virus was closely related to viruses detected in wild birds in the region and in ongoing H5N1 outbreaks in poultry from British Columbia.
      • Changes observed in the virus sequence from the patient may indicate an increased ability to bind human receptors; but those changes, identified as a mixture of mutations, may have been generated by replication of the virus in the patient rather than transmitted at the time of infection. Though concerning, the changes would be more troubling if identified in animal hosts or in an early human upper respiratory tract infection when mutations might facilitate human-to-human transmission.
      • There is no evidence of human-to-human transmission with this case.

Influenza A(H5) Human Cases – Virus Sequences to Date
Genetic sequences in the current H5N1 strains maintain primarily avian genetic characteristics and lack the genetic changes that would make the virus better adapted to infect or spread among humans. CDC continues to monitor influenza A(H5N1) viruses for concerning changes, including those that would signal an increased ability to infect humans, to be transmitted person-to-person, or indicate that currently available diagnostics, antiviral treatments, or candidate vaccine viruses would be less effective. To date, no such changes have been identified.

Symptom Monitoring Recommendations
All people with direct or close exposure to H5N1 infected animals should be monitored during exposure, and for 10 days after exposure.

  • State and local health departments are monitoring workers on impacted farms and can facilitate testing and treatment.

Common signs/symptoms include:

  • Feeling feverish, cough, sore throat, runny or stuffy nose, muscle/body aches, headaches, fatigue, eye redness (or conjunctivitis), shortness of breath or difficulty breathing.

If signs/symptoms develop, patient is to:

  • Seek medical evaluation for possible testing and antiviral treatment.
  • Isolate away from others during evaluation.

Ongoing Human Monitoring
CDC is continuing to support state and local health departments monitoring exposed people.

  • For people with known exposure, more than 8,000 people have been monitored, more than 390 people have been tested, and 55 cases have been detected for targeted H5 surveillance.
  • Since February 2024, 61,000 people have been tested for influenza and, using an algorithm that would have detected H5N1 or another novel virus, 2 cases of H5N1 have been identified.

Seroprevalence Study
Surveys and serologic testing among workers on impacted dairy farms in Michigan and Colorado support the need for active outreach about infection risks and preventive practices in languages that workers speak. They also highlight the need for active monitoring and testing in real-time by state and local health partners.

  • In the surveys and testing, 8 of 115 workers showed evidence of previous HPAI A(H5) infections.
    • Of those, all spoke Spanish, all cleaned milking parlors or had milked cows, none wore respiratory protection, and a minority wore eye protection.

Ferret Studies
Studies of the pathogenesis and transmission of human influenza A(H5N1) viruses in ferrets have shown that 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% vs. 100%)
  • Both show some capacity to transmit via respiratory droplets.

The Michigan human A(H5N1) virus better represents currently circulating viruses, compared with the Texas human A(H5N1) virus.

[The CDC Influenza Risk Assessment Tool (IRAT) is included in the presentation slides but was not discussed in the meeting, owing to time. The tool can be accessed at https://www.cdc.gov/pandemic-flu/php/national-strategy/influenza-risk-assessment-tool.html.]

Public Health Risk

  • Overall risk to the public for HPAI A(H5N1) remains low.
  • There is greater risk for people with close, prolonged, or unprotected exposures to infected animals or contaminated environments.

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H5N1 Vaccines and Current Strategies – Kimberly Armstrong, PhD, MT (ASCP), Supervisory Health Scientist, Director, Influenza and Emerging Infectious Diseases Division (IEIDD), Biomedical Advanced Research and Development Authority (BARDA), Administration for Strategic Preparedness and Response (ASPR)

BARDA’s H5N1 Preparedness Program – Kimberly Armstrong, PhD, MT (ASCP)
The Biomedical Advanced Research and Development Authority (BARDA) is part of the Administration for Strategic Preparedness and Response (ASPR) and makes medical countermeasures available for public health emergencies. This includes partnering with companies, academics, and other organizations to develop vaccines, diagnostics, and therapeutics for a variety of threats.

  • To address gaps in pandemic preparedness, BARDA considers:
    • Vaccine doses and delivery
    • Better, flexible influenza vaccines
    • Treatments for all spectrums of disease

BARDA was formed in 2005 and has grown the U.S. pandemic influenza vaccine response capabilities from no effective capability (2 U.S.-licensed seasonal vaccines with one technology) to having a 1st dose pandemic vaccine in 2 to 3 months for known viruses, or in 4 to 5 months for novel viruses, and 660M doses in ~7 months, which would enable protection of everyone in the United States.

  • There have also been improvements in the U.S. flu vaccine infrastructure (e.g., manufacturers, technologies, FDA-approved pandemic vaccines and stockpiled components).
  • There are still gaps to meeting the goals in the national biodefense strategy, which include protection of the entire U.S. population within 130 days.

National Pre-pandemic Influenza Vaccine Stockpile (NPIVS)
To advance timely vaccination strategies to mitigate the next pandemic, the BARDA preparedness program has available an NPIVS, and a library of influenza viruses and vaccine seeds that can kickstart the next pandemic response.

  • NPIVS is currently composed of adjuvants and pre-pandemic influenza virus bulk antigen and final containers of vaccine manufactured from candidate vaccine viruses, representing virus subtypes regarded to have the greatest potential to cause a pandemic.
  • BARDA has pre-existing contracts with 3 vaccine manufacturers: CSL Seqirus, GSK, and Sanofi.
    • Each vaccine manufacturer has licensed pandemic vaccines with varying doses, delivery mechanisms, and antigen types.
  • mRNA-based vaccines are not a part of the current preparedness activities, owing to licensing issues, but BARDA will re-assess their inclusion in the future, based on licensing.

BARDA’s Influenza A(H5) Virus Clade 2.3.4.4b Preparedness
In January 2022, the initial detections of influenza A(H5) in wild birds and, subsequently, in commercial poultry kicked off the BARDA preparedness response.

  • BARDA contracted with vaccine manufacturers to begin commercial manufacturing of vaccines.
  • Throughout the next few years, BARDA contracted with manufacturers to develop clinical trials and developed its own clinical trials, as well. BARDA-sponsored clinical trials began enrolling in the fall of 2024.
  • Even though the risk to the public remains low, BARDA is continuing to prepare, through procurement and vendor-managed inventory, in case that changes.

BARDA has funded clinical trials with various manufacturers:

  • GSK: an observer-blind, randomized clinical trial investigating 2 doses of antigen and 2 doses of adjuvant in different combinations, with the primary endpoint of safety and immunogenicity.
  • CSL Seqirus: a multi-center, randomized, observer-blind study testing an Astrakhan H5N1 vaccine to evaluate safety and immunogenicity.
  • BARDA-sponsored: a randomized, double-blind study testing the safety and immunogenicity of A/H5 inactivated monovalent influenza vaccines at different antigen dose levels adjuvanted with AS03 or MF59.

BARDA continues to work with numerous partners, including CDC and WHO, to foster seed development, bulk production, clinical trials, stockpile and stability programs, pre-EUA living documents, and faster to first doses and full immunization plans.

QUESTIONS & ANSWERS

Q: Do we have an H5N1 vaccine? Do we anticipate one soon?
Kimberly Armstrong (BARDA/ASPR): It will really depend on what the clinical data says. FDA has to review the clinical data and make sure it would be sufficient for licensure. And then, of course, we would want ACIP to also make a recommendation on who we would target that vaccine for. So, the data will determine when an H5 vaccine will become available soon.

Q: If the tanks that you mentioned are tested weekly and must have negative tests each time, does that mean that no milk from that tank can be used or processed for three weeks?
Kathleen Harriman (CDPH): That’s right. I mean that they aren’t off quarantine until they’ve had three negative tests over three weeks.

Q: Do dairy cattle workers have access to running water and are they able to wash their hands in their work area?
Kathleen Harriman (CDPH): Sometimes. Maybe. I don’t know, exactly. I suspect the restrooms there would be running water. Whether there are in what they call “the milking parlor,” I honestly don’t know. Somebody who works there could tell you better, but I suspect it’s not optimal.
L.J Tan (Immunize): Yeah, I would probably agree. But Tom, have you got any data on that? Like, how easy is it for them to actually do simple things like washing their hands?
Tom Shimabukuro (CDC): I don’t have a good answer for that. I assume it may be variable depending on the farm.

Q: Are asymptomatic cows shedding virus in milk in the affected herds? And the question obviously has to do with how useful would it be to move only the symptomatic cows and keep using the asymptomatic cows.
Kathleen Harriman (CDPH): I believe they can use milk from asymptomatic cows. It’s the cows that are in the hospital pen whose milk is not permitted to be used. That’s my understanding. I could be wrong, so don’t quote me, but that’s my understanding. You don’t know about asymptomatic cows: if there’s asymptomatic infection and shedding virus.
L.J Tan (Immunize): So, another question was about whether they’re shedding virus, and you don’t know, so that’s good to know.

Q: What about seasonal vaccination of farm workers, obviously potentially preventing humans as a mixing vehicle?
Kathleen Harriman (CDPH): Yes, a lot of thought has been put into that. But, right now, most of these farms are quarantined and under biosecurity. So you can’t really get on the farms and then it’s access issues. And I think there’s all kinds of issues in terms of even, if a local health department wanted to find, vaccinators who have a contract to go out, even that’s been a problem. These are rural areas.
L.J Tan (Immunize): Tom, what about other states? What are you seeing?
Tom Shimabukuro (CDC): I think the main reason to vaccinate farm workers is not that different than vaccinating just the general population, which is to prevent influenza and complications from influenza. Individual protection from seasonal influenza is the main reason to vaccinate farm workers or to vaccinate anybody. Specifically on the farms, there may be some benefit to reducing the incidence of respiratory illness from influenza, so you kind of reduce that signal-to-noise ratio if you are monitoring for H5N1 infection. The issue of preventing co-infection and, therefore, reassortment, I think, is largely theoretical and speculative. I do think, when we talk about vaccinating farm workers, the main thing is to protect them from influenza and the serious complications from influenza.

Q: If you pasteurize the milk, then is it safe to drink?
Kathleen Harriman (CDPH): Yes.

Q: Regarding the pediatric case in California, given the mild symptoms and typical presentation and lack of exposure that you saw, what prompted the subtype testing in the first place?
Kathleen Harriman (CDPH): It was just an academic lab that had just developed this H5 subtyping test on their own and just had requested that all influenza A swabs that were in identified in any of the clinics associated with that system be sent. So, it was almost random, honestly, how it was detected.
Tom Shimabukuro (CDC): I’ll just add that over the summer, CDC had this enhanced summer influenza surveillance where we asked healthcare providers and healthcare facilities and public health partners, state labs to maintain a high level of vigilance and surveillance. And, just to kind of outline how this happens, I think the California case is a little bit different but, just in general, if somebody comes in with a respiratory illness and they’re tested for influenza and they’re tested with a test which can subtype for H1N1 or H3N2, and that test comes back un-subtype-able, that sort of initiates this algorithmic approach that I was talking about where if you have an un-subtype-able test, then it goes to a lab, like a public health lab at the county or the state, where they can perform additional subtyping using the CDC assay. If they get a positive H5, that’s considered a presumptive positive, and then the procedure is to send that to the CDC lab for confirmatory testing.

Q: We should know whether asymptomatic cows are shedding virus, if they’ve been exposed in the herd; when will we know the answer to that?
Tom Shimabukuro (CDC): I don’t think that’s a question that Kim or Kathleen or I can answer with any degree of confidence. We’d have to get our USDA or state agricultural partners on here to answer that. I’m just not comfortable answering a question on animal health like that. It’s more a USDA question.
L.J Tan (Immunize): The Summit will probably reach out to some of our partners at USDA and see if we can get an answer.

Q: Regarding the Canadian case, the mutations have resulted in a strain that probably could be transmitted human-to-human. Although it’s not transmitted that way, could it be possible that the teen would be the one that could start human-to-human transmission?
Tom Shimabukuro (CDC): The virus that was detected in the case in Canada did have some changes that may indicate an increased ability to bind human receptors. But, given the stage of illness when this person was tested from the onset of symptoms until the time they were tested and the severity of illness, there was a mixture of mutations, and these may have been generated by replication of this patient with advanced disease rather than the time of infection. These viruses still are primarily avian in origin and appear to be difficult to transmit human-to-human. And, although it was concerning to see that, they would be more concerning if these were identified in animal hosts and were circulating widely in animal hosts or they were detected in human upper respiratory tract specimens earlier in the course of disease where there may be more of an opportunity to transmit human-to-human. But, right now, there was an extensive contact tracing that the British Columbia health authorities did and there’s no evidence of any human-to-human transmission with that case or with any other cases.

Q: Is there any effort to try to – I mean, obviously you can’t vaccinate poultry back in the past – but what about vaccinating cattle with H5N1 vaccine?
Tom Shimabukuro (CDC): I think that’s a USDA question. They regulate the animal vaccines.
Kimberly Anderson (BARDA/ASPR): Yes, they regulate the animal vaccines.

Q: Regarding concern about H5N1 infection in the immunocompromised person, is that a risk because they would have potentially prolonged infection with prolonged generation of new human-adapted H5N1?
Tom Shimabukuro (CDC): I think people with underlying medical conditions would be at increased risk for more severe outcomes, if they were infected. I don’t know if that places them at any increased risk of getting infected. I think what we know from the current outbreak is that certain occupational groups or certain occupational groups that perform specific functions, when they come into contact with animals or contact with contaminated materials, they are at highest risk for getting infection. But I think it’d be reasonable to think that if you had underlying health conditions and you were infected, that may place you at increased risk for more severe outcomes.

Q: Is stockpiling of N95 masks part of the pandemic preparedness plan at ASPR?
Kimberly Anderson (BARDA/ASPR): There is a stockpile, but it is limited. So some of these have been made available to states that may need them to protect these at-risk workers. So, yes, there is a stockpile, but you go through them very fast when there is a pandemic.

Q: Can you provide an update on the DRC outbreak?
Tom Shimabukuro (CDC): I don’t have any other information than what’s publicly available through media reports.

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