Avian Influenza A(H5N1) Infection in a Texas Dairy Farm Worker

“Sporadic human infections with highly pathogenic avian influenza (HPAI) A(H5N1) virus, with a wide spectrum of clinical severity and a cumulative case fatality of more than 50%, have been reported in 23 countries over more than 20 years. HPAI A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds worldwide since 2020–2021, resulting in outbreaks in poultry and other animals. Recently, HPAI A(H5N1) clade 2.3.4.4b viruses were identified in dairy cows, and in unpasteurized milk samples, in multiple U.S. states.” https://www.nejm.org/doi/full/10.1056/NEJMc2405371.

This article in the New England Journal of Medicine now provides us with a clinical case report of the infected Texas dairy farm worker.

In late March, the farm worker developed redness and discomfort in his right eye. The worker denied having any fever, chills, cough, shortness of breath or loss or distortion of vision.

The worker denied any contact with dead or diseased birds or poultry. He did report close contact with cows, including cows that were showing signs of possible infection with avian influenza manifested by lethargy, fever, decreased appetite, dehydration, and/or decreased milk production. He did routinely wear gloves, but no other PPE including masks or eye protection.

On physical examination, the patient did not appear severely ill. His lungs were clear.

His eye examination revealed the following:

We are looking at the patient facing us, so the eye on the left side of this photo is actually his right eye, and the eye to our right is actually his left eye. Looking at his left eye, he has conjunctivitis (inflammation of the conjunctiva, which is the superficial lining of the eye and eye lids). We can see that it is red and injected, meaning that we see the blood vessels much more prominently than in someone with a normal-appearing eye. His right eye demonstrates a subconjunctival hemorrhage, in other words, there is bleeding directly under the conjunctiva. We can tell that there is a hemorrhage (bleeding) because the redness is confluent and obscures the blood vessels, whereas in his left eye, we can see the blood vessels much more clearly.

The examiner swabbed the patient’s nose and right eye to test for influenza virus. The test (which looks for genetic traces of virus) of both samples was positive for influenza A and for the H5 protein, which is indicative of avian influenza. That test also suggested that the amount of virus in the eye sample was very high. The CDC performed additional testing that confirmed that the virus was A(H5N1) and genetically the same as the virus detected to be circulating among dairy cows.

The patient was instructed to isolate at home and was started on an oral antiviral medication (oseltamivir). Over the ensuing days, the patient’s conjunctivitis resolved and no family members developed signs or symptoms of infection.

Additional testing of the virus genetic material revealed that it had not mutated in a way that would change the receptor-binding protein from the avian form (α2,3-linked sialic acid [we do have this form or receptors in our eyes]) to the human form (α2,6-linked sialic acid [this is the receptor type in the human respiratory tract]). On the other hand, the virus retrieved from the infected farm worker had acquired a mutation in the PB2 protein that has been associated with adaptation of the bird virus to mammals, including humans. Fortunately, the virus did not have the mutations that we associate with developing resistance to our usual influenza A virus antiviral agents.

My commentary:

This is good news/bad news. The bad news is that apparently cows can transmit the virus to humans who are in close and prolonged contact with infected cows, though we still don’t know how transmission occurred – respiratory droplets from infected cows? Contact with virus in the milk of infected cows and then touching or rubbing one’s eyes? Aerosolization of virus from the milk when cleaning floors or equipment used in milking the cows?

The good news is that the patient did well and appeared to recover well, the virus did not show worrisome changes that would suggest that the virus can now efficiently transmit to and among humans, and the patient did not appear to infect anyone in his household, though we were not provided with any information as to what precautions were used in the home and how many persons were in the home.

There remain many questions besides those I have already raised. One question is whether the antiviral treatment prevented him from becoming more ill and/or did it shorten his course of illness? I also hope that they will carefully follow this farm worker over time. We know that in other mammals, this virus has seemed to produce significant neurological disease. The eyes can be a route for viruses to access the brain. It would be good to follow this patient to ensure he does not develop any signs of neurological disease in the future.