Avian Influenza A (H5N1) in Cats, Cows, and Humans: Symptoms, Timeline, Antiviral Therapies, and Vaccine Development - A Comprehensive Review

Key risks and prevention measures for avian influenza A(H5N1)

Apr 07, 2024

Geese, grackles, cows goats and cats can be infected with H5N1 and it is particularly deadly for cats.

H5N1 Avian Influenza: A Critical Update

H5N1 has now been detected in dairy cows in multiple states in the United States. A human case in Texas linked to this outbreak underscores the potential for this deadly virus to jump species. Here's what you need to know.

What Is Avian Influenza?

Avian Influenza, also known as bird flu, is a highly contagious viral disease that has mostly affected domestic and wild birds. More recently it is infecting more mammal species, including humans. Beyond its impacts on animal health, the disease has devastating effects on the poultry industry, threatening workers’ livelihoods, food security, and international trade. The H5N1 strain is of particular concern due to its high mortality rate and the risk of adaptation allowing for easier human-to-human transmission.

Between 2003 and 2023, there were a total of 878 confirmed cases of H5N1 virus infection, resulting in 458 deaths, indicating a fatality rate of approximately 52%. Throughout this period, the majority of cases occurred in Asia and Africa, with notable hotspots in China (53 cases), Egypt (359 cases), and Indonesia (200 cases). From 2020 to July 2023, H5N1 infections in humans were reported in a variety of countries, including Laos (1 case), India (1 case), the United Kingdom (4 cases), China (2 cases), the United States (1 case), Vietnam (1 case), Spain (2 cases), Ecuador (1 case), Chile (1 case), and Cambodia (2 cases). These recent cases collectively resulted in more than three deaths. It's worth noting that this zoonotic virus has spread to new geographic areas, including South America. (1)

Currently, there is no evidence suggesting human-to-human transmission of the virus, however, with the growing rate of transmission among cows across multiple states, the risk of transmission to humans is increasing. The more humans infected, the greater the risk of viral evolution that could enable human-to-human transmission.

It's crucial to recognize that one of the deadliest influenza viruses in history, the Spanish influenza (1918–1919), originated from an avian influenza virus that adapted to infect humans. This occurred at a time when international air travel didn’t exist. The U.S. interstate highway system didn’t exist yet. This historical precedent underscores the importance of considering the potential for spillover when assessing the risk posed by the current virus.

Recent Developments

Infections in More Mammals: Since 2021, H5N1 has spread globally among wild birds, leading to infections in cats, skunks, goats, cows, and humans.
Second Human Case in the U.S.: In early April 2024, the second human case of H5N1 in the United States was reported in Texas. Thankfully, the individual exhibited only mild symptoms (conjunctivitis) and recovered after antiviral treatment.

We'll track the sequence of events involving H5N1 and examine the symptoms exhibited in humans, cows, birds, and cats, all of which have been affected by the virus. Additionally, we'll delve into the evolution of the virus, discuss potential vaccine candidates and treatments, and provide a comprehensive overview of the current situation.

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TimeLine

Birds to Cats, Goats, Cows and Humans

Nearly 900 human cases were reported worldwide from earlier H5N1 variants since 2003 resulting in a 52% mortality rate.
Since 2020, 12 human cases of avian influenza A(H5N1) clade 2.3.4.4b virus detections have been reported to WHO, four of which were severe cases and eight were mild or asymptomatic.

2021

December 2021: Human cases of the predominant H5N1 strain occurred in the U.K.

2022

April 30, 2022: The first human case of H5N1 (bird flu) in the US was reported in a Colorado inmate. An inmate contracted the virus during work release at a Montrose County farm euthanizing an infected flock. The patient experienced fatigue as the sole symptom, was treated with oseltamivir, and has since recovered.
2022: Over 2,500 individuals exposed to H5N1-infected birds were tracked; only one case was detected. Other individuals involved in the culling operation tested negative and underwent retesting as a precaution.
2022: USDA monitoring avian influenza spread across 30 states, affecting over 35 million birds. Over 22 million birds were culled to contain the outbreak, primarily in Iowa; an additional 2.1 million were affected in Nebraska.
“Avian influenza can kill entire flocks of birds so this causes devastating losses for the farming sector” Dr. Keith Hamilton, Head of the WOAH Preparedness and Resilience Department (2)

2023

Cats were infected with the H5N1, 2.3.4.4b variant. “An outbreak of H5N1 bird flu in household cats was reported by the World Health Organization, underscoring that these viruses can infect and cause illness in household pets. Thirty-four domestic cats across eight provinces in Poland tested positive for avian influenza A(H5N1) virus (“H5N1 bird flu”). Many of the infected cats showed neurological signs (e.g., paralysis, seizures) and became severely ill or died.”
Of the 25 cats for which the information is available, two were outdoor cats, 18 were indoor with access to a balcony, terrace, or backyard, and five were indoor cats with no access to the outside environment. Seven cats are reported to have had the opportunity for contact with wild birds.
This is the first report of high numbers of cats infected with avian influenza A(H5N1) spread over a wide geographical area within any country.

2024

February 23, 2024: A skunk tested positive for H5N1 in New Mexico
March 8, 2024: A goat tested positive in Minnesota
March 25, 2024: The USDA announces the detection of highly pathogenic avian influenza (H5N1) in samples taken from dairy cows at two farms in Kansas and two in Texas. This marks the first occurrence of H5N1 in cattle in the United States.
Unpasteurized milk from infected cows also tests positive, but officials assure the public of the safety of commercial milk, as pasteurization effectively deactivates the virus. Milk from affected cows will be disposed of.
March 28: Dairy cows in Idaho test positive for bird flu after receiving cattle from another state, indicating potential cow-to-cow transmission, according to the state's agriculture department.
March 29: A dairy herd in Michigan tests positive for bird flu after receiving cows from Texas, further suggesting cow-to-cow transmission of the virus.
April 1: The USDA confirms bird flu in dairy cows in New Mexico, along with five additional dairy herds in Texas. This brings the total number of outbreaks to 12 in just over a week.
April 1: Texas reports the first human case of H5N1 bird flu linked to this outbreak. The patient, who had contact with infected cows, experiences only minor symptoms such as conjunctivitis, or pink eye.
April 3: USDA confirms H5N1 presence at suspected dairy farm in Idaho.
April 3: Ohio Department of Agriculture reports an outbreak, confirmed by USDA as the same virus. A farm in Ohio received cows from an infected Texas farm on March 8, indicating virus circulation weeks before initial outbreak detection on March 25.
The CDC says the health risk for the general public is considered low but people in close contact with infected animals (including livestock) are at greater risk of infection.
There are no confirmed reports of death loss in dairy cattle directly attributed to these detections. Most sick cows begin recovering within a few days.

Symptoms in Humans, Cows, Poultry, and Wild Birds

Symptoms of H5N1 in Humans

While infection is relatively rare in humans, it's essential to be aware of the symptoms:

Common:
- Fever and chills
- Cough
- Sore throat
- Muscle aches
- Eye redness /Conjunctivitis/ Pink eye
  Note: Keep in mind that bacterial conjunctivitis is frequently seen in only one eye and generally has thicker eye discharge, while viral conjunctivitis often affects both eyes symmetrically with thinner, more watery discharge.
- Runny or stuffy nose
- Headaches
- Fatigue
- Difficulty breathing/shortness of breath
- Diarrhea
- Nausea
- Vomiting
Severe Complications
- Pneumonia
- Acute respiratory distress syndrome
- Neurological symptoms (confusion, seizures)

Symptoms in Dairy Cows

Decreased lactation
Low appetite

Symptoms in poultry (chickens, turkeys)

Sudden death of bird with no clinical symptoms
Lack of energy
Inappetence
Swelling of the head, comb, eyelid, wattles, and hocks
Discoloration of wattles, combs, and legs
Nasal discharge
Coughing
Sneezing
Neurological signs (incoordination)
Diarrhea

Symptoms in Wild Birds

Neurological signs (incoordination, swimming in circles, weak)
Sudden death

Symptoms in Cats

Respiratory symptoms (coughing, sneezing)
Neurological signs (seizures, paralysis), or a combination of both.
The infection can be fatal.

Pet Owners

Pet owners need to be aware that dogs and cats can contract bird flu, particularly if they come into contact with infected birds or their droppings. While the risk of you catching bird flu directly from your pet is low, it's still a possibility. For instance, a veterinarian in New York City contracted a mild form of bird flu (influenza A(H7N2) virus) in 2016 after treating sick cats without protective gear. (3)

Treatment of Humans

Antiviral Medications: Early treatment with antiviral medications (such as oseltamivir or zanamivir) is crucial to reduce the severity of illness and prevent complications. These medications may also be given as a preventative measure to those in close contact with infected birds or people.
The historical problem has been that doctors do not identify the virus fast enough, resulting in more severe symptoms and death. Reports of severe avian influenza A(H5N1) illness in humans have included fulminant pneumonia leading to respiratory failure, acute respiratory distress syndrome, septic shock, and death.

Vaccine Development

The HA protein is targeted by neutralizing antibodies produced during infection or vaccination.
The virus from the human specimen closely resembles two pre-pandemic candidate vaccine viruses: IDCDC-RG71A and IDCDC-RG78A.
There are only four amino acid changes (L104M, L115Q, T195I, V210A) between the HA1 of the Texas virus and the A/Astrakhan/3212/2020-like CVV.
Only two changes (L115Q, T195I) are observed when compared to the A/American wigeon/South Carolina/22-000345-001/2021-like CVV.
These changes are not in major antigenic epitopes.
Antibodies elicited by vaccines based on A/Astrakhan/3212/2020-like and A/American wigeon/South Carolina/22-000345-001/2021-like viruses would likely cross-react and provide protection against the Texas virus.
These are vaccine candidates that have not been developed or approved yet.

The Evolution of H5N1

The H5N1 virus has a history of spillover from birds to humans, causing severe respiratory illness with a high mortality rate (currently 52%).
Genetic Adaptation: Viruses can change (mutate) as they replicate within a host. Certain adaptive mutations, such as PB2-E627K seen in the Texas human case, might improve the virus's ability to infect and replicate in humans, but it hasn’t caused human-to-human transmission when found in earlier human infections of H7N9.
Surveillance: Continued surveillance of H5N1 and its evolving genetic characteristics is necessary to assess the ongoing risk to humans and inform preventative strategies.

Risk Assessment

Overall Low Risk: The overall risk of H5N1 infection for the general public remains low. However, those in close contact with birds, and cows are at higher risk. (poultry, dairy or beef farmers, veterinarians, and wildlife workers)
Concern of Mutation: The virus's ongoing evolution in infected people and the wider variety of infected mammals raises serious concerns. The most significant risk is H5N1 adapting to easily spread among humans, potentially leading to a new pandemic.

What You Can Do

Vigilance: Stay informed and be aware of local H5N1 outbreaks and guidance. Report unusual sickness or death in birds to state or wildlife authorities.
Precautions for High-Risk Groups: People in regular close contact with birds or cows should take precautions such as wearing protective gear (gloves, N-95 masks) and practicing good hygiene (handwashing).
People in close contact with cows or birds must be aware of the fact that cats in these environments are also highly susceptible.
Safe Food Handling: Always cook meats, poultry, and eggs thoroughly to kill any potential viruses. Avoid unpasteurized milk and undercooked meat products.

TACT’s Overview

The recent transmission of H5N1 among cows and other mammals, including humans, highlights the ever-present risk of another pandemic. While the current risk to the general public is low, continuous surveillance, precautionary measures, and preparedness are essential. Should this or any other avian influenza virus gain the ability to easily spread between humans, the risk of a pandemic becomes very real.

We may have a few years before human-to-human transmission occurs but risk is growing at an exponential rate with the transmission to cows and goats, making the odds of more human infections very likely. If the virus finds someone with a weakened immune system, where it has more time to evolve within a human, then the odds of it mutating to enable human-to-human transmission increase. Unfortunately, with millions affected by COVID-19, and the resulting weakened immune system, we are inadvertently paving the way for H5N1's continued evolution.

It is more important than ever to implement measures preventing airborne transmission in various settings such as schools, hospitals, and businesses. Strengthening airborne infection control protocols in transportation, especially air travel, is extremely important. We must take proactive measures to stop the next pandemic while actively working to mitigate the damage of COVID-19, and other airborne respiratory pathogens. Investing in systems and policies that prevent the spread of airborne pathogens will protect the lives of millions of people, ensuring a brighter and happier future.

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