High-pathogenicity avian influenza (HPAI) is a contagious viral influenza infection in cattle, domestic poultry, wild birds, and other domestic and wild mammals. HPAI virus is also a zoonotic pathogen. As of October 2024, the identified strain in cattle is influenza A subtype H5N1. Common clinical signs in affected cattle include transient fever, listlessness, decreased appetite and rumination, dehydration, changes in fecal consistency, respiratory signs, and decreased milk production and/or a change in milk consistency in lactating cows. Diagnosis is based on clinical signs, PCR assay, serological testing, and virus isolation. Treatment consists of supportive care, along with identification and treatment of comorbidities or secondary disease. Control measures include increased emphasis on biosecurity, premovement testing, and continuous monitoring for sick cattle.
High-pathogenicity (aka highly pathogenic) avian influenza (HPAI) in cattle induces high morbidity rates (up to 40%, with an average range of 10–20%). Mortality rates are low (less than 5% reported); however, infected herds are at increased risk for elective culling due to failure to return to predisease milk production levels.
Clinical signs have been documented primarily in lactating dairy cattle and develop over approximately 2–3 weeks. Mammary, digestive, and respiratory systems are primarily impacted. HPAI has been detected in milk and nasal swabs via PCR assay, in mammary glands and lungs on postmortem examination, and in muscle tissue at slaughter.
As of October 2024, disease outbreaks in 333 dairy herds had been reported to the USDA and confirmed as HPAI by the National Veterinary Services Laboratories (NVSL) in Texas, Kansas, Michigan, New Mexico, Idaho, Ohio, North Carolina, South Dakota, Colorado, Wyoming, Minnesota, Iowa, Oklahoma, and California.
Species affected include cattle, domestic poultry (chickens, turkeys, quail), wild birds, and a variety of domestic and wild mammals, including domestic cats, big cats in captivity, mice, desert cottontails, prairie voles, wild bobcats and mountain lions, bears (brown, black, and polar), bottlenose dolphins, gray and harbor seals, coyotes, red foxes, martens, mink, fishers, river otters, squirrels, raccoons, skunks, and opossums.
Etiology of High-Pathogenicity Avian Influenza in Cattle
Avian influenza viruses are type A orthomyxoviruses (Alphainfluenzavirus influenzae or influenza A virus) characterized by antigenically homologous nucleoprotein and matrix internal proteins, which are identified by serological testing such as agar gel immunodiffusion (AGID) or ELISA. Avian influenza viruses are further divided into 16 hemagglutinin (H1–H16) and 9 neuraminidase (N1–N9) subtypes.
Epidemiology of High-Pathogenicity Avian Influenza in Cattle
The epidemiology of HPAI in cattle is under investigation. The whole genome sequence of the virus suggests that virus spilled over from wild birds to dairy cattle.
Transmission and incubation period of HPAI are also under investigation. The movement of apparently healthy lactating cows from one geographic location to another has revealed cow-to-cow transmission. Proposed mechanisms of viral transmission within a herd or from herd to herd include the following:
direct contact with milk (milk from infected cattle contains high levels of virus)
inhalation of aerosolized virus and aerosolized spread to neighboring sites
indirect transfer by fomites (eg, workers and visitors, equipment, vehicles)
Morbidity and Mortality
Feedback from monitoring clinically affected cows suggests that disease may develop slowly over several days to weeks or follow a bell curve. The curve may peak a week or more after the first clinical signs of disease appear. At the peak, 5–60% of the herd can be clinically affected.
A retrospective review of clinically affected herds showed that up to 15% of affected cattle may die or be euthanized due to primary or secondary disease or comorbidity. As of October 2024, following HPAI infection, a variable percentage of cattle is electively culled due to failure to return to production. Following infection, production in many herds falls below baseline or projected historical levels, with some herds falling by up to 30%.
Zoonotic Risk of High-Pathogenicity Avian Influenza in Cattle
As of October 2024, HPAI infection had been confirmed in 17 humans associated with exposure to sick or infected dairy cows in the US. Clinical signs ranged from conjunctivitis to mild flulike clinical signs and acute respiratory illness. All 17 recovered.
The primary risk factor for HPAI infection in humans is contact with or infected dairy cattle.
People working closely with infected or potentially infected cattle, birds, or other animals are at risk for infection and should take proper precautions, including protecting the eyes, covering the nose and mouth, wearing gloves, laundering outerwear, and washing hands before eating or using tobacco. They should also use personal protective equipment (PPE), avoid exposure to sick or dead animals, and exercise caution when handling raw milk, feces, and bedding from suspected or confirmed sick animals.
Clinical Findings of High-Pathogenicity Avian Influenza in Cattle
Clinical signs, disease severity, and morbidity and mortality rates of HPAI in cattle vary.
From head to tail, the following clinical signs have been observed:
scleral injection
increased skin tenting time
reddened nares and nasal mucosa
increased nasal discharge, including serous, mucopurulent, and/or bloody nasal secretions
increased salivation
inappetence/decreased feed consumption
increased respiratory rate and effort
subcutaneous emphysema
decreased rumen fill
decreased milk production
more concentrated, thicker milk consistency and color change (yellow to gray) with variable increases in somatic cell count
vasculitis of the vaginal vestibule
change in fecal consistency, including maldigestion and firm feces with increased mucus to diarrhea
fever early in the course of clinical signs (39–42ºC [103–108ºF])
Cattle affected with HPAI are commonly diagnosed as off feed, lethargic, and febrile. They may present with normal milk, with mastitis in one or more quarters, or with a thicker, creamier milk secretion. Visually, the udder may appear as if the cow is drying off (decreased udder fill). Fecal and respiratory changes may be subtle or absent.
Herds monitoring individual animals via wearable technologies show a precipitous decrease in rumination time in minutes, rebounding but not returning to baseline minutes, and decreased physical activity (as measured by number of steps taken).
Anecdotally reported reproductive signs include abortions in mid-to-late gestation and a decreased number of animals in estrus during weeks with the highest level of clinical disease.
Diagnosis of High-Pathogenicity Avian Influenza in Cattle
Molecular assay with follow-up testing
Serological testing
Virus isolation for influenza A
After onset of clinical signs, the gold standard test for diagnosis of HPAI at the time of this publication is molecular assay (PCR or RT-PCR assay) on milk for influenza A matrix. Not all quarters may be shedding, so collecting from all 4 quarters in a composite sample is important. For surveillance purposes, milk string/pen or bulk milk tank samples can be collected.
For dry cows, heifers, and calves, nasal swabs are the preferred diagnostic test.
Pearls & Pitfalls
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Follow-up testing for H5N1 (H5.2.3.4.4.b) and confirmation occurs at an NVSL site. Serological (serum antibody) testing is another surveillance method. More research is being conducted in this area because cows exposed to infection may not all consistently produce an immune response. A nasal or conjunctival swab can be collected for PCR assay from nonlactating animals or those that develop primary respiratory signs.
The Federal Order issued by the Animal Plant and Health Inspection Service (APHIS), USDA, effective April 29, 2024, established the framework for required testing for interstate movement and for reporting both PCR-positive milk samples and positive influenza A serological tests.
HPAI must be differentiated from other causes of high-morbidity disease, including infectious and environmental causes of respiratory disease, mastitis, and indigestion or diarrhea. Further investigation must also include reasons for decreased milk production, including management, feed, and animal husbandry factors.
Lesions
No pathognomonic lesions or specific gross antemortem lesions have been observed or defined in cattle with HPAI. Generalized vasculitis of mucous membranes, including the ocular conjunctiva and sclera, inside the nares, and the vaginal vestibule, has been observed.
Treatment of High-Pathogenicity Avian Influenza in Cattle
Supportive care
Treatment of HPAI centers around hydrating the patient, supporting the rumen, and decreasing fever. Support includes feeding free choice hay or long-stemmed forage and administering oral drench and IV fluids, probiotics, injectable B vitamins to stimulate appetite, and transdermal or IV flunixin for fever associated with acute bovine mastitis and bovine respiratory disease, per label instructions.
Prevention of High-Pathogenicity Avian Influenza in Cattle
Biosecurity practices are being reviewed to understand the introduction and spread of HPAI in cattle. Measures include limiting access to essential personnel and creating designated locations for visitors, vehicles, and equipment. In addition, before being introduced to the herd, cattle should be tested, isolated, and monitored for 30 days.
Key Points
HPAI infection in cattle primarily impacts the mammary, digestive, and respiratory systems.
Diagnosis is by detection of viral RNA or antibodies against influenza A and can be confirmed with virus isolation.
Epidemiology and prevention are being investigated.
Zoonotic infections are rare but have been reported. Infections in humans can remain subclinical or be accompanied by conjunctivitis, respiratory disease, and other mild clinical signs of influenza.
For More Information
USDA Animal and Plant Health Inspection Service. Detections of highly pathogenic avian influenza (HPAI) in livestock.
US Food & Drug Administration. Updates on highly pathogenic avian influenza (HPAI).
Centers for Disease Control and Prevention. Current H5N1 bird flu situation in dairy cows.
Schwabenlander S, Lombard J, Christensen B, et al. US Department of Agriculture. 2024 Highly pathogenic avian influenza (H5N1) - Michigan dairy herd and poultry flock summary.
Burrough ER, Magstadt DR, Petersen B, 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;30(7):1335-1343.
Caserta LC, Frye EA, Butt SL, et al. From birds to mammals: spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle led to efficient intra- and interspecies transmission, United States, 2024. Nature. Published online July 25, 2024.
Ngyuen TQ, Hutter C, Markin A, et al. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. United States, 2024. BioRxIV. Preprint posted online May 1, 2024.
Baker AL, Arruda B, Palmer MV, et al. Dairy cows inoculated with highly pathogenic avian influenza virus H5N1. Nature, Accepted manuscript. Published online October 15, 2024.
