#18,110
In the fall of 2022 when H5N1 began spreading rapidly through a large mink farm in Spain (see Eurosurveillance: HPAI A(H5N1) Virus Infection in Farmed Minks, Spain, October 2022). That particular strain had acquired a rare mutation (PB-T271A), which is believed to `enhance the polymerase activity of influenza A viruses in mammalian host cells and mice'.Last summer, the CDC issued an IRAT Risk Assessment On Mink Variant of Avian H5N1, finding it's scores had risen in 6 of the 10 parameters used to evaluate their zoonotic potential (see chart below).
While the Texas B3.13 genotype which as infected cattle and at least 3 humans does not contain this PB-T271A mutation, there are other amino acid changes that could conceivable increase the virus's transmissibility, and so the CDC had embarked on a similar set of experiments.
Today, the CDC has released the following report, and while it finds the Texas does not currently spread efficiently via the respiratory route (1 in 3, or 33% were infected), it is readily spread via direct contact and is quite lethal in ferrets.
Of course, 33% is a long way from zero, so prolonged contact with someone who is infected might still result in transmission. But for now, it appears to have a ways to go before it can begin spreading in a sustained and efficient manner in humans.
That, of course, could change over time. And given its lethality in ferrets, it deserves our respect.
The CDC's report follows.
June 7, 2024—CDC has completed its initial study of the effects of the A(H5N1) bird flu virus from the human case in Texas on ferrets, a model used to assess potential impact on people.
- The A(H5N1) virus from the human case in Texas caused severe illness and death in ferrets. A(H5N1) infection in ferrets has been fatal in the past. This is different from what is seen with seasonal flu, which makes ferrets sick, but is not lethal.
- The A(H5N1) virus from the human case in Texas spread efficiently between ferrets in direct contact but did not spread efficiently between ferrets via respiratory droplets. This is different from what is seen with seasonal flu, which infects 100% of ferrets via respiratory droplets.
- These findings are not surprising and do not change CDC’s risk assessment for most people, which is low. The results do reinforce the need for people who have exposure to infected animals to take precautions and for public health and agriculture communities to continue to work together to prevent the spread of the virus to additional dairy herds and people.
CDC researchers used a ferret model[1] to better understand the severity of illness and efficiency of transmission of A/Texas/37/2024. For decades, CDC has conducted these types of studies to inform risk assessments of influenza viruses with pandemic potential. CDC used the virus from the human case in Texas which was reported on April 1, 2024, and was associated with sick dairy cow exposure. These are the first publicly reported animal model findings from a virus that infected a human as part of the current multistate outbreak of A(H5N1).
The study, completed on Friday, May 31, found that A/Texas/37/2024 virus caused severe disease (100% lethal) in all six ferrets that were infected. This is consistent with what has been found recently in ferret studies with A(H5N1) viruses, including two published studies conducted in the past year. Ferrets infected with A(H5N1) viruses from mink in Spain (A/mink/Spain/3691-8_22VIR10586-10/2022) and from a person in Chile (A/Chile/25945/2023) had severe illness that was either fatal or required euthanasia.
In terms of spread, the CDC ferret study found that the A/Texas/37/2024 virus spread easily among ferrets (3 of 3 ferrets, or 100%) in direct contact with infected ferrets (placed in the same enclosure). However, the virus was less capable of spreading by respiratory droplets, which was tested by placing infected ferrets in enclosures next to healthy ferrets (with shared air but without direct contact).
In that situation, only 1 of 3 ferrets (33%) became infected, and there was a one- or two-day delay in transmission with the A/Texas/37/2024 virus compared to transmission with seasonal flu viruses. This suggests that A/Texas/37/2024-like viruses would need to undergo changes to spread efficiently by droplets through the air, such as from coughs and sneezes. CDC is repeating the experiment to confirm the findings and the results of these experiments will be used to inform an ongoing, broader CDC-led influenza risk assessment (IRAT) on A/Texas/37/2024.
In terms of direct contact spread, the mink virus from Spain caused efficient spread (100%) among ferrets. The study using the Chile virus found 75% spread by direct contact among ferrets. While the findings related to respiratory transmission were similar in that there was no efficient respiratory spread, there were differences in terms of whether any respiratory spread was observed or not.
The study cited previously using A/mink/Spain/3691-8_22VIR10586-10/2022found 37.5% transmission by respiratory droplets. The study using A/Chile/25945/2023found no transmission by respiratory droplets. The most recent CDC findings are more consistent with the findings with the mink virus from Spain than the virus from Chile. (Additional information about ferret transmission findings with avian influenza is available below.)
Taken together, these findings underscore that the A(H5N1) viruses spreading in poultry, dairy cows, and other animals with sporadic human infections pose a serious potential public health risk and could cause serious illness in people. While the three cases of A(H5N1) in the United States have been mild, it is possible that there will be serious illnesses among people.
Findings from this study are largely consistent with recent A(H5N1) studies in ferrets, as well as past reports of serious human illness resulting from this virus. These findings also suggest; however, that current A(H5N1) viruses would need to undergo genetic changes to spread more easily via respiratory droplets, which is reassuring. Efficient respiratory droplet spread, like what is seen with seasonal influenza viruses, is needed for sustained person-to-person spread to happen. These findings do not change CDC’s immediate risk assessment for the general public who do not have animal exposures, which is low.
There have been several prior respiratory droplet spread in ferrets with avian influenza viruses. Selected studies:
- A study done using the avian influenza A(H7N9) virus (which has the highest pandemic risk assessment score on CDC’s Influenza Risk Assessment Tool (IRAT)) found that “A/Hong Kong/125/2017” spread easily among ferrets in the same enclosure but only 1 of 3 ferrets in the adjacent enclosure became via respiratory droplets in that study.
- A 2006 CDC study summarized results of a ferret study on A/Hong Kong/486/97, an A(H5N1) virus isolated from a human case in 1997. That study found respiratory droplet spread occurred in 2 of the 3 ferrets (66%). At that time, A(H5N1) viruses had caused probable person-to-person spread. That older 1997 A(H5N1) virus did not emerge to spread efficiently among people. Person-to-person spread has not been observed with A(H5N1) viruses since 2007.
- The previously mentioned 2024 study evaluated an A(H5N1) virus that caused an outbreak among mink at a mink farm in Spain (“A/mink/Spain/3691-8_22VIR10586-10/2022”) and found that respiratory droplet spread occurred in 3 out of 8 ferrets (37.5%). Of note, this study used a side-to-side airflow methodology; by contrast, CDC uses a top-to-bottom airflow approach. Despite the differences in methods, the results from this study were similar to those found in the CDC study.
- The most recently published CDC A(H5N1) ferret study was conducted on a virus from a human A(H5N1) case in Chile. Investigators found efficient direct contact spread, but no respiratory droplet spread.
- On the lowest end of the pandemic risk assessment scale, another ferret study looked at the effects of a low pathogenic avian influenza A(H7N9) virus (A/chicken/Tennessee/17-007431-3/2017) isolated from a multistate poultry outbreak in the United States with no human infections. There was inefficient spread in the direct contact model, with only 1 of 3 co-housed ferrets becoming infected. Because spread in the direct contact model was inefficient, spread by respiratory droplets was not studied.
Ferrets are considered the best small mammal for studying influenza virus infection and transmission and are commonly used as a tool to inform public health risk assessments of emerging influenza viruses. In these studies, ferrets are experimentally infected and followed to assess severity of illness. To test the ability of the virus to spread, infected ferrets are exposed to healthy ferrets in different settings. Understanding the disease characteristics of novel influenza viruses and their capacity to spread is a critical component of any public health response.
