The US Faces an H5N1 Outbreak: What Do We Know About It?

Bird flu virus outbreak, avian influenza, farmer with chicken.

(Adobe Stock 830193791 by Berit Kessler)

Avian influenza, or bird flu, has caused multiple pandemics over the years, the most recent being the 2009 swine flu pandemic involving the H1N1 strain. In recent years, a new strain of highly pathogenic avian influenza, H5N1, has been circulating among various species. More recently, it has affected dairy cattle in the US, but is it a cause of concern?

What Is Avian Influenza?

Avian Influenza viruses are a type of Influenza A Virus. These negative sense, single-stranded RNA viruses belong to the family Orthomyxoviridea. Two of its main surface glycoproteins play an important role in pathogenesis-Hemagglutinin (HA) and Neuroaminadase (NA). Hemagglutinin binds to sialic acid receptors in humans' respiratory tract and alveolar type II cells to cause infection.¹

Avian influenza viruses are divided into 2 groups based on their pathogenicity- Low pathogenic avian influenza and High pathogenic avian influenza (HPAI). Low pathogenic avian influenza virus has a low mortality rate and cannot infect easily, while High Pathogenic Avian Influenza has a high mortality rate, can cross intestinal and respiratory barriers, and damages the tissues of birds.² H5N1 is a High Pathogenic Avian Influenza Virus that can affect multiple species.³

When Were the First Cases in Cattle Reported?

In February 2024, veterinarians in the US were informed of a syndrome affecting lactating dairy cattle in northern Texas. The cattle experienced reduced feed intake, rumination, and an abrupt drop in milk production. The milk of the affected animals was thick and creamy yellow, similar to colostrum. Affected farms reported a peak incidence 4 to 6 days after the first animals were affected. Though lab tests (blood, urine, feces, milk, and nasal swab samples) and postmortem tests were conducted, they failed to show a conclusive cause of the illness.⁴

Farms in Kansas and New Mexico reported similar cases in early March 2024. Deaths of wild birds and domestic cats who were fed milk from sick cows were also reported in affected farms in Texas. The US Department of Agriculture National Veterinary Services Laboratory could later confirm that the affected animals were infected with Highly Pathogenic Avian Influenza H5N1.⁴ As of July 18, 2024, 13 states have been affected by outbreaks in dairy cows, and 48 states have been affected by outbreaks in poultry.⁵

Why Is Avian Flu Affecting Cattle?

While avian flu, especially H5N1 and others, can affect other species, cattle were not considered a host for this Highly pathogenic avian influenza. A recent study found sialic acid (SA) receptors in dairy cattle's respiratory tract and mammary glands. The respiratory tract had both SA α2,3-galactose and SAα2,6-galactose, but unlike humans, SAα2,6-gal is mainly confined to the sub-epithelial region of the trachea.

However, SA α2,3-galactose continued to be expressed on the epithelium of the bronchi to alveolar pneumocytes, making it possible for avian influenza to infect the lower respiratory tract of cattle. The mammary glands of cattle also expressed both SA α2,3-gal-β GalNAc (MAL-II) and SAα2,6-gal (SNA) receptors. While the exact cause of mastitis in dairy cattle affected by HPAI H5N1 is unclear, an initial investigation showed strong epitheliotropism in the mammary glands.⁶

Can H5N1 Affect Humans?

While there is generally a low risk of humans getting infected by avian influenza, sporadic cases have occurred when humans were in close and prolonged contact with birds and cattle in recent cases.6 The first reported case of H5N1 in humans was in May 1973, and as of July 23, 2024, more than 890 people were reportedly infected with H5N1.⁷

The first human-to-human transmission of H5N1 was confirmed in 2005 in Thailand after an 11-year-old girl transmitted the disease to her mother and aunt.8 When infecting a host, the H5N1 virus has a receptor preference like other Influenza A viruses. Human Influenza viruses bind to 2,6 linked sialic acids in the upper respiratory tract. In contrast, the avian influenza viruses bind to sialic acids through^2,3 links present on the ocular epithelium and type II alveolar cells.¹

On April 1, 2024, the Texas Department of State Health Services reported that a farm worker had tested positive for high pathogenic avian influenza H5N1 after being in contact with infected dairy cattle. The worker developed conjunctivitis and was treated with Oseltamivir and was asked to isolate following CDC guidelines.⁹ On May 22, 2024, the Michigan Department of Health and Human Services reported the second cause of a presumed cow-to-human transmission of H5N1 transmission.¹⁰

The third reported case of H5N1 in the US was the first to report respiratory symptoms, with the previous 2 cases complaining only of conjunctivitis. The third patient reported signs of upper respiratory tract infection, such as cough without fever and eye discomfort with watery discharge.¹¹ There are currently no human deaths from the recent H5N1 outbreak in the US. A total of 13 cases have been confirmed in the US from April 2024 to 25th July 2024, with Colorado reporting the highest number of cases.¹²

Is It Safe to Consume Dairy in the US?

Although milk from infected cows is diverted and not included in the food supply chain, HPAI H5N1 was detected in raw milk from infected cows. A small study by the US Food and Drug Administration (FDA) consisting of 297 pasteurized milk samples from 17 states found viral RNA by qrRT-PCR in 20.2% of the samples. However, it is important to note that while viral RNA was found, no infectious virus was detected in these samples. A positive qrRT-PCR simply means that viral RNA entered the milk supply, but it cannot be determined if this virus was ever infectious.¹³

While the majority of the milk in the US is pasteurized and, hence, safe to drink, it is not advised to drink raw milk as it can contain bacteria and viruses, including H5N1, and can cause serious illness.

Do We Have a Vaccine Against H5N1?

In 2021, the FDA approved a multidose vial formulation of AUDENZ, making it the first-ever adjuvanted, cell-based influenza vaccine. The FDA had previously approved a single-dose prefilled formulation of the same vaccine. However, this vaccine is currently unavailable to the general public and is only reserved for individuals aged 6 months and above who are at an increased risk for H5N1.¹⁴

Influenza A viruses can cause pandemics due to the plasticity and segmentation of their genome, making them more susceptible to acquiring mutations. Most avian influenza viruses affect birds, but some, like H5N1 and H1N1, affect multiple species. The current findings of sialic receptors in dairy cattle show that avian influenza may have other hosts.

While the risk of animal-human or bird-human transmission of H5N1 remains relatively small for the general population, the recent increase in H5N1 infections in various species may pose a risk for a pandemic. Increasing cases among animals and birds and an increase in hosts should prompt a discussion on managing a possible pandemic in the future.

References

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14. CSL Seqirus. FDA Approves Multi-Dose Vial Presentation for AUDENZ. CSL Seqirus US. https://www.cslseqirus.us/news/fda-approves-multi-dose-vial-presentation-for-audenz