A growing, but incomplete, picture of affected States
#18,033
The CDC's EID Journal published an expedited research paper today on preliminary findings into the infection and spread of HPAI H5N1 clade 2.3.4.4b among both cattle and domestic cats in the United States.
Infected cattle appear to suffer relatively mild, nonspecific illness, but shed copious amounts of the virus in their milk.
Cats, however, often develop severe neurological manifestations leading to rapid death , similar to what we've seen with other mammals (see PrePrint: HPAI H5N1 Infections in Wild Red Foxes Show Neurotropism and Adaptive Virus Mutations ).
The authors note a number of antemortem clinical signs observed in affected cats, including: `. . . depressed mental state, stiff body movements, ataxia, blindness, circling, and copious oculonasal discharge. Neurologic exams of affected cats revealed the absence of menace reflexes and pupillary light responses with a weak blink response.'
Due to its length, I've only posted the link, abstract, and some excerpts. Follow the link to read the report in its entirety. I'll have brief postscript after the break.
Research
Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024
Eric R. Burrough, Drew R. Magstadt, Barbara Petersen, Simon J. Timmermans, Phillip C. Gauger, Jianqiang Zhang, Chris Siepker, Marta Mainenti, Ganwu Li, Alexis C. Thompson, Patrick J. Gorden, Paul J. Plummer, and Rodger Main
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.
Highly pathogenic avian influenza (HPAI) viruses pose a threat to wild birds and poultry globally, and HPAI H5N1 viruses are of even greater concern because of their frequent spillover into mammals. In late 2021, the Eurasian strain of H5N1 (clade 2.3.4.4b) was detected in North America (1,2) and initiated an outbreak that continued into 2024. Spillover detections and deaths from this clade have been reported in both terrestrial and marine mammals in the United States (3,4). The detection of HPAI H5N1 clade 2.3.4.4b virus in severe cases of human disease in Ecuador (5) and Chile (6) raises further concerns regarding the pandemic potential of specific HPAI viruses.
In February 2024, veterinarians were alerted to a syndrome occurring in lactating dairy cattle in the panhandle region of northern Texas. Nonspecific illness accompanied by reduced feed intake and rumination and an abrupt drop in milk production developed in affected animals. The milk from most affected cows had a thickened, creamy yellow appearance similar to colostrum. On affected farms, incidence appeared to peak 4–6 days after the first animals were affected and then tapered off within 10–14 days; afterward, most animals were slowly returned to regular milking. Clinical signs were commonly reported in multiparous cows during middle to late lactation; ≈10%–15% illness and minimal death of cattle were observed on affected farms. Initial submissions of blood, urine, feces, milk, and nasal swab samples and postmortem tissues to regional diagnostic laboratories did not reveal a consistent, specific cause for reduced milk production. Milk cultures were often negative, and serum chemistry testing showed mildly increased aspartate aminotransferase, gamma-glutamyl transferase, creatinine kinase, and bilirubin values, whereas complete blood counts showed variable anemia and leukocytopenia.
In early March 2024, similar clinical cases were reported in dairy cattle in southwestern Kansas and northeastern New Mexico; deaths of wild birds and domestic cats were also observed within affected sites in the Texas panhandle. In >1 dairy farms in Texas, deaths occurred in domestic cats fed raw colostrum and milk from sick cows that were in the hospital parlor. Antemortem clinical signs in affected cats were depressed mental state, stiff body movements, ataxia, blindness, circling, and copious oculonasal discharge. Neurologic exams of affected cats revealed the absence of menace reflexes and pupillary light responses with a weak blink response.
(SNIP)
Discussion
This case series differs from most previous reports of IAV infection in bovids, which indicated cattle were inapparently infected or resistant to infection (9). We describe an H5N1 strain of IAV in dairy cattle that resulted in apparent systemic illness, reduced milk production, and abundant virus shedding in milk. The magnitude of this finding is further emphasized by the high death rate (≈50%) of cats on farm premises that were fed raw colostrum and milk from affected cows; clinical disease and lesions developed that were consistent with previous reports of H5N1 infection in cats presumably derived from consuming infected wild birds (10–12).Although exposure to and consumption of dead wild birds cannot be completely ruled out for the cats described in this report, 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.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.Horizontal transmission of HPAI H5N1 virus has been previously demonstrated in experimentally infected cats (13) and ferrets (14) and is suspected to account for large dieoffs observed during natural outbreaks in mink (15) and sea lions (16). Future experimental studies of HPAI H5N1 virus in dairy cattle should seek to confirm cross-species transmission to cats and potentially other mammals.
(SNIP)
The susceptibility of domestic cats to HPAI H5N1 is well-documented globally (10–12,25–28), and infection often results in neurologic signs in affected felids and other terrestrial mammals (4). Most cases in cats result from consuming infected wild birds or contaminated poultry products (12,27). The incubation period in cats is short; clinical disease is often observed 2–3 days after infection (28). Brain tissue has been suggested as the best diagnostic sample to confirm HPAI virus infection in cats (10), and our results support that finding. One unique finding in the cats from this report is the presence of blindness and microscopic lesions of chorioretinitis. Those results suggest that further investigation into potential ocular manifestations of HPAI H5N1 virus infection in cats might be warranted.
The genomic sequencing and subsequent analysis of clinical samples from both bovine and feline sources provided considerable insights. The HA and NA sequences derived from both bovine milk and cat tissue samples from different Texas farms had a notable degree of similarity. Those findings strongly suggest a shared origin for the viruses detected in the dairy cattle and cat tissues.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. Although pasteurization of commercial milk mitigates risks for transmission to humans, a 2019 US consumer study showed that 4.4% of adults consumed raw milk >1 time during the previous year (29), indicating a need for public awareness of the potential presence of HPAI H5N1 viruses in raw milk.
Ingestion of feed contaminated with feces from wild birds infected with HPAI virus is presumed to be the most likely initial source of infection in the dairy 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 (30). HPAI H5N1 viruses are well adapted to domestic ducks and geese, and ducks appear to be a major reservoir (31); however, terns have also emerged as an important source of virus spread (32). The mode of transmission among infected cattle is also unknown; however, horizontal transmission has been suggested because disease developed in resident cattle herds in Michigan, Idaho, and Ohio farms that received infected cattle from the affected regions, and those cattle tested positive for HPAI H5N1 (33). Experimental studies are needed to decipher the transmission routes and pathogenesis (e.g., replication sites and movement) of the virus within infected cattle.
In conclusion, we showed that dairy cattle are susceptible to infection with HPAI H5N1 virus and can shed virus in milk and, therefore, might potentially transmit infection to other mammals via unpasteurized milk. A reduction in milk production and vague systemic illness were the most commonly reported clinical signs in affected cows, but neurologic signs and death rapidly developed in affected domestic cats.HPAI virus infection should be considered in dairy cattle when an unexpected and unexplained abrupt drop in feed intake and milk production occurs and for cats when rapid onset of neurologic signs and blindness develop. The recurring nature of global HPAI H5N1 virus outbreaks and detection of spillover events in a broad host range is concerning and suggests increasing virus adaptation in mammals. Surveillance of HPAI viruses in domestic production animals, including cattle, is needed to elucidate influenza virus evolution and ecology and prevent cross-species transmission.
Dr. Burrough is a professor and diagnostic pathologist at the Iowa State University College of Veterinary Medicine and Veterinary Diagnostic Laboratory. His research focuses on infectious diseases of livestock with an emphasis on swine.
Since 2020 we've seen increased HPAI H5Nx spillover into mammalian species, with many displaying severe neurological symptoms prior to death.
Travel Med. & Inf. Dis.: Pacific and Atlantic Sea Lion Mortality Caused by HPAI A(H5N1) in South America
While HPAI H5N1 has most often been a respiratory infection in humans, we have seen several case reports over the years describing severe neurological presentations.
A 2009 PNAS study (Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration) found that the H5N1 virus was highly neurotropic in lab mice, and in the words of the authors `could initiate CNS disorders of protein aggregation including Parkinson's and Alzheimer's diseases’.
In a 2015 Scientific Reports study on the genetics of the H5N1 clade 2.3.2.1c virus - Highly Pathogenic Avian Influenza A(H5N1) Virus Struck Migratory Birds in China in 2015 – the authors described its neurotropic effects, and warned that it could pose a ` . . . significant threat to humans if these viruses develop the ability to bind human-type receptors more effectively.'
While clinical details of many H5Nx human infections have gone unpublished, almost 18 months ago, in Clinical Features of the First Critical Case of Acute Encephalitis Caused by Avian Influenza A (H5N6) Virus, we learned of the severe neurological impact of the virus on a 6 year-old girl in China.
While certainly not the typical presentation of H5Nx infection in humans, the authors wrote:
In view of the fact that the clinical manifestations of this novel H5N6 reassortant are acute encephalitis, rather than previous respiratory symptoms, once these reassortants obtained the ability of human-to-human transmission through reassortment or mutations, it will bring great health threat for humans.
While we can't really know what H5Nx pandemic would look like, last September we looked at a study (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans) that warned:
- Highly pathogenic avian influenza (HPAI) H5Nx viruses can cause neurological complications in many mammalian species, including humans.
- Neurological disease induced by HPAI H5Nx viruses in mammals can manifest without clinical respiratory disease.
- HPAI H5Nx viruses are more neuropathogenic than other influenza A viruses in mammals.
- Severe neurological disease in mammals is related to the neuroinvasive and neurotropic potential of HPAI H5Nx viruses.
- Cranial nerves, especially the olfactory nerve, are important routes of neuroinvasion for HPAI H5Nx viruses.
- HPAI H5Nx viruses have a broad neurotropic potential and can efficiently infect and replicate in various CNS cell types.
- Vaccination and/or antiviral therapy might in part prevent neuroinvasion and neurological disease following HPAI H5Nx virus infection, although comprehensive studies in this area are lacking.
But even without a neurological component, HPAI H5Nx has an impressive record of causing severe illness and death, and is not to be taken lightly.
