Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024

Abstract

We report highly pathogenic avian influenza A(H5N1) virus in dairy cattle and cats in Kansas and Texas, United States, which reflects the continued spread of clade 2.3.4.4b viruses that entered the country in late 2021. Infected cattle experienced nonspecific illness, reduced feed intake and rumination, and an abrupt drop in milk production, but fatal systemic influenza infection developed in domestic cats fed raw (unpasteurized) colostrum and milk from affected cows. Cow-to-cow transmission appears to have occurred because infections were observed in cattle on Michigan, Idaho, and Ohio farms where avian influenza virus-infected cows were transported. Although the US Food and Drug Administration has indicated the commercial milk supply remains safe, the detection of influenza virus in unpasteurized bovine milk is a concern because of potential cross-species transmission. Continued surveillance of highly pathogenic avian influenza viruses in domestic production animals is needed to prevent cross-species and mammal-to-mammal transmission.

Keywords: H5N1; HPAI; United States; avian influenza; bovine influenza A; cats; clade 2.3.4.4b; dairy cattle; highly pathogenic avian influenza A(H5N1); influenza; respiratory infections; spillover; viruses; zoonoses.

Figure 1

Mammary gland lesions in cattle in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. A, B) Mammary gland tissue sections stained with hematoxylin and eosin. A) Arrowheads indicate segmental loss within open secretory mammary alveoli. Original magnification ×40. B) Arrowheads indicate epithelial degeneration and necrosis lining alveoli with intraluminal sloughing. Asterisk indicates intraluminal neutrophilic inflammation. Original magnification ×400. C, D) Mammary gland tissue sections stained by using avian influenza A immunohistochemistry. C) Brown staining indicates lobular distribution of avian influenza A virus. Original magnification ×40. D) Brown staining indicates strong nuclear and intracytoplasmic immunoreactivity of intact and sloughed epithelial cells within mammary alveoli. Original magnification ×400.

Figure 2

Lesions in cat tissues in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Tissue sections were stained with hematoxylin and eosin; insets show brown staining of avian influenza A viruses via immunohistochemistry by using the chromogen 3,3′-diaminobenzidine tetrahydrochloride. Original magnification ×200 for all images and insets. A) Section from cerebral tissue. Arrowheads show perivascular lymphocytic encephalitis, gliosis, and neuronal necrosis. Inset shows neurons. B) Section of lung tissue showing lymphocytic and fibrinous interstitial pneumonia with septal necrosis and alveolar edema; arrowheads indicate lymphocytes. Inset shows bronchiolar epithelium, necrotic cells, and intraseptal mononuclear cells. C) Section of heart tissue. Arrowhead shows interstitial lymphocytic myocarditis and focal peracute myocardial coagulative necrosis. Inset shows cardiomyocytes. D) Section of retinal tissue. Arrowheads show perivascular lymphocytic retinitis with segmental neuronal loss and rarefaction in the ganglion cell layer. Asterisks indicate attenuation of the inner plexiform and nuclear layers with artifactual retinal detachment. Insets shows all layers of the retina segmentally within affected areas have strong cytoplasmic and nuclear immunoreactivity to influenza A virus.

Figure 3

Phylogenetic analysis of hemagglutinin gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate different clades. Red text indicates the virus gene sequences from bovine milk and cats described in this report, confirming those viruses are highly similar and belong to H5 clade 2.3.4.4b. The hemagglutinin sequences from this report are most closely related to A/avian/Guanajuato/CENAPA-18539/2023|EPI_ISL_18755544|A_/_H5 (GISAID, https://www.gisaid.org) and have 99.66%–99.72% nucleotide identities.

Figure 4

Phylogenetic analysis of neuraminidase gene sequences in study of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Colors indicate different subtypes. Red text indicates the virus gene sequences from bovine milk and cats described in this report, confirming those viruses belong to the N1 subtype. The neuraminidase sequences from this report had 99.52%–99.59% nucleotide identities to sequences from viruses isolated from a chicken and wild birds in 2023.