Cows infected with H5N1 avian influenza had mild illness characterized by a drop in milk production, but cats fed raw milk experienced severe systemic disease with high mortality, researchers found.
The findings, published in CDC's Emerging Infectious Diseases, come from an analysis of samples from farms in Kansas and Texas taken in mid-March. They suggest cow-to-cow transmission of H5N1, and raise concerns about consumption of raw milk as a potential transmission mechanism, Eric Burrough, DVM, PhD, of Iowa State University College of Veterinary Medicine in Ames, Iowa, and colleagues reported.
"The recurring nature of global ... H5N1 virus outbreaks and detection of spillover events in a broad host range is concerning and suggests increasing virus adaptation in mammals," the researchers wrote. "Surveillance of [highly pathogenic avian influenza] HPAI viruses in domestic production animals, including cattle, is needed to elucidate influenza virus evolution and ecology and prevent cross-species transmission."
Veterinarians in the U.S. first sounded the alarm on an odd illness affecting dairy cattle in the panhandle region of northern Texas in February 2024. These cows had an abrupt drop in milk production, and what they did produce was thickened and creamy yellow in appearance, similar to colostrum, the milk produced in the first days after a delivery. The cows had reduced appetite, but the majority recovered within 10 to 14 days, the researchers reported.
By early March, similar cases were soon reported in dairy cattle in southwestern Kansas and northeastern New Mexico, and at least one dairy farm in Texas reported deaths among cats that drank raw milk from sick cows.
In mid-March, the Iowa State University Veterinary Diagnostic Laboratory received samples from dairy cattle in Texas and Kansas, and two dead cats from a Texas dairy farm. Samples tested positive for H5N1, prompting the U.S. Department of Agriculture to issue a press release not long thereafter.
Disease in Cows
Burrough and colleagues reported that milk and mammary gland samples had very low cycle threshold (Ct) values for H5N1, indicating a high viral load.
Some, but not all, animals had firm mammary glands, typical of mastitis, and the chief microscopic lesion seen in affected cows was acute multifocal neutrophilic mastitis, they reported.
While the mode of transmission isn't known, cow-to-cow transmission has been suggested because cattle herds in Michigan, Idaho, and Ohio that received infected animals have also tested positive for H5N1, according to the study.
Burrough and colleagues wrote that feed contaminated with feces from infected wild birds is the most likely source of infection on diary farms.
"Although the exact source of the virus is unknown, migratory birds (Anseriformes and Charadriiformes) are likely sources because the Texas panhandle region lies in the Central Flyway, and those birds are the main natural reservoir for avian influenza viruses," they wrote.
They noted that influenza A-related declines in milk production have occurred among dairy cattle in the past: in Japan in 1949, and in Europe in 1997-1998 and 2005-2006. "The sporadic occurrence of clinical disease in dairy cattle worldwide might be the result of changes in subclinical infection rates and the presence or absence of sufficient baseline [influenza A virus] IAV antibodies in cattle to prevent infection," the researchers wrote.
Disease in Cats
Among about 24 domestic cats that were fed milk from sick cows on a north Texas dairy farm, more than half became sick and died in mid-March.
They had signs of systemic influenza infection, including depressed mental state, stiff body movements, ataxia, blindness, circling, and copious oculonasal discharge, the researchers reported. Neurological examination found no menace reflexes and pupillary light responses with weak blink response.
Two animals were available for postmortem analysis. Brain and lung samples had low Ct values, again indicating a high viral load in these animals, they reported.
They also found mild hemorrhages in the subcutaneous tissues over the dorsal skull, along with multifocal meningeal hemorrhages in the cerebrum. Microscopic lesions were consistent with severe systemic virus infection, including evidence of meningoencephalitis, pneumonia, myocarditis, and chorioretinitis.
Burrough and colleagues called the findings of blindness and chorioretinitis "unique," suggesting that "further investigation into potential ocular manifestations of HPAI H5N1 virus infection in cats might be warranted."
While eating dead wild birds can't be ruled out as the source of transmission to cats, "the known consumption of unpasteurized milk and colostrum from infected cows and the high amount of virus nucleic acid within the milk make milk and colostrum consumption a likely route of exposure," the researchers wrote.
"Therefore, our findings suggest cross-species mammal-to-mammal transmission of HPAI H5N1 virus and raise new concerns regarding the potential for virus spread within mammal populations," they concluded.
Burrough and coauthors added that hemagglutinin and neuraminidase sequences from both cows and cats at different Texas farms had "a notable degree of similarity," strongly suggesting a "shared origin."
"Further research, case series investigations, and surveillance data are needed to better understand and inform measures to curtail the clinical effects, shedding, and spread of HPAI viruses among mammals," they wrote.
The H5N1 clade involved in this outbreak is 2.3.4.4b, which was first reported in the U.S. in late 2021, the researchers noted. It has been involved in other recent reports of mammal spillover in the U.S., including in seals in New England and a host of terrestrial animals including 50 red foxes, six skunks, four raccoons, two bobcats, two opossums, one coyote, one fisher, and a gray fox. An outbreak of H5N1 among farmed mink in Spain also raised concerns in 2022.
Disclosures
The authors reported no financial conflicts of interest.
Primary Source
Emerging Infectious Diseases
Source Reference: Burrough ER, et al "Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024" Emerg Infect Dis 2024; DOI: 10.3201/eid3007.240508.
https://www.medpagetoday.com/infectiousdisease/uritheflu/109885
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