June 14, 2024—A new CDC study reports what happened when the eyes of ferrets were experimentally exposed to an avian influenza A(H5N1) ("A(H5N1) bird flu") virus isolated from a human case that occurred in 2023 in Chile. The study found:

The ferrets experienced severe disease with fever and weight loss;
The ferrets´ nasal specimens contained detectable virus, and the ferrets were able to spread virus to healthy ferrets via direct contact; and,
After infection, virus was found outside of the respiratory tract, including in the intestinal tract, the central nervous system, as well as the eyes of the ferrets.
Ferrets are an animal model often used to assess the potential impact of respiratory diseases on people.

The virus used in this study, A/Chile/25945/2023 HPAI A(H5N1), was isolated from a severe human case identified in March 2023 in the South American nation of Chile. It is closely related to the virus that is causing a multistate outbreak of A(H5N1) virus in U.S. dairy cows with three sporadic human infections. Two of the three infected people in the United States reported eye redness and discomfort (consistent with conjunctivitis) after exposure to sick cows; the third person had mild respiratory illness. All three have since recovered. No human-to-human spread of the virus has been identified, and CDC believes the immediate risk to the public is low. People who have work or recreational exposures to infected animals are at higher risk of infection.

The findings from this study highlight the potential for A(H5N1) viruses to cause infection in people after exposure to virus via the eyes. Tear fluid provides an opportunity for virus to spread from the eyes to nasal/respiratory tract through the tear ducts and vice versa. The findings also underscore the importance of eye protection when working around infected animals or potentially contaminated environments or liquids/surfaces, like raw milk.

Previous CDC research has shown that this same virus from Chile caused severe and fatal disease in ferrets that were experimentally exposed through the nose and/or direct contact settings with infected ferrets. That study found no ferret-to-ferret spread of the virus from Chile via respiratory droplets.

In this study, published on June 12 in the journal Emerging Microbes & Infections, researchers tested whether ferrets exposed to A/Chile/25945/2023 via the eyes became infected with the virus and were similarly capable of spreading it in a direct contact setting. Researchers placed a healthy ferret in the enclosure of each infected ferret; collected nasal, rectal, and conjunctival specimens from all animals over the course of seven days; and assessed virus replication within and beyond the respiratory tract. Infectious virus was detected in either nasal swab or rectal swab specimens from all six previously healthy ferrets that had been co-housed with infected ferrets, four of which developed severe disease and were humanely euthanized.

While most infections with influenza viruses result in respiratory disease, conjunctivitis (eye infection) has been associated with previous human infections with avian influenza A viruses and is part of the current CDC case definition for A(H5N1) virus surveillance. Possible explanations for how infection via the eyes might occur include:

contamination of the eye(s), potentially with a splash of contaminated fluid, such as milk; high levels of A(H5N1) virus have been found in unpasteurized milk from H5N1-infected cows.
touching the eye(s) with something contaminated with A(H5N1) virus, such as a hand.
virus-containing aerosols expelled from infected people during breathing, coughing, or sneezing.
This study, the first to evaluate the ability of clade 2.3.4.4b A(H5N1) viruses to cause disease following a non-respiratory entry portal, builds on close to two decades of CDC research investigating the role of infection via the eyes in the spread of influenza viruses and the progression of disease. The findings underscore the ability of influenza viruses to cause infection following non-respiratory exposures and the importance of CDC´s ongoing efforts to inform and educate people who work with dairy cows, or other potentially infected animals, about actions they can take to reduce their risk of exposure, including by wearing personal protective equipment like gloves, masks, and goggles or face shields. Last week, CDC posted a web spotlight summarizing other work in ferrets using the virus from the human case of H5N1 in Texas.