Avian Influenza Update

Part III

The A(H5N1) avian influenza outbreak investigation continues to unfold, and we are rapidly gaining new information. This is the third in a series of current updates on the avian influenza outbreaks on U.S. dairy farms.

1.      A study planned for publication in July was released early by the CDC (kudos for that!) entitled: “Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024.” Early Release – Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus Infection in Domestic Dairy Cattle and Cats, United States, 2024 – Volume 30, Number 7—July 2024 – Emerging Infectious Diseases journal – CDC.

We have learned a lot and I have previously written about the signs of infection in dairy cattle. However, until now, we had been provided with little information on how the disease manifested in cats, other than mentions of neurological defects and rapid decline with resulting death in six cats that were fed milk from infected cows on the farms with outbreaks. This study provides many more details. We are told that the cats manifested a depressed mental state, stiff body movements, uncoordinated movements, loss of vision, a tendency to repetitively move in circles, and abundant drainage from their eyes and nostrils. On examination, the infected cats had lost their menace reflexes (these are reflex movements of the head and eyes in response to a perceived threat that is often tested by the examiner covering one eye and moving their hand quickly towards the other eye without making contact with the cat), which generally suggests some neurological defect between the eye and the neuropathways to the brain. These cats also had a weak blink response and had lost their pupillary light response (the reaction of the pupils of the eye when a light in directed at it) suggesting a neurological defect between the eye and the brainstem of the cats. These findings together suggest very severe neurological impairment.

We also are learning the specifics of some cow deaths. We had previously been given the impression that all of the cows that were infected suffered only mild illness. However, some recent statements seemed to imply that there must have been one or more deaths of cows due to infection. This study indicates that they reviewed tissues from necropsies performed on three cows that were euthanized (suggesting that they must have had more severe disease) and on three cows that died of natural causes, which I take to mean cows that survived and recovered from the infection, but then died for reasons attributed to their advanced age.

The tissue examination of the cows showed mastitis (inflammation of their mammary glands) in the majority of cases and hepatitis (liver inflammation) in three of the cows.

The tissue examination from the cats showed much more severe disease with severe inflammation in the central nervous system and inflammation of their lungs (interstitial pneumonia), heart (myocarditis) and eyes (chorioretinitis). Further, tests for detecting the antigens of the influenza virus were positive in all of these tissues.

Genetic sequencing of the virus from the cows and cats shows a high degree of similarity tying these infections epidemiologically. The authors conclude: “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.”

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. Texas is in the Central Flyway for these migratory birds that are the primary hosts and reservoirs of avian influenza. It remains unclear how cattle are transmitting the virus to other cattle, if such transmission is occurring as suspected (due to the spread of infection in herds in other states after cows were moved from one of the Texas dairy farms with an outbreak to these dairy farms).

The authors conclude with this statement: “The recurring nature of global HPAI H5N1 virus outbreaks and detection of spillover events in a broad host range is [sic] concerning and suggests increasing virus adaptation in mammals.”

• Confirmed outbreaks are now in 9 states: Texas, New Mexico, Colorado, Kansas, Idaho, South Dakota, Michigan, Ohio and North Carolina.

• At the beginning of  last week, the U.S. Department of Agriculture (USDA) announced that it will begin testing of ground beef in states with bird flu outbreaks, and recently warned the virus may be passing back and forth between cattle and poultry farms. 

• Another concerning development has been to see very sharp increases in influenza A in wastewater testing form a number of geographically distributed sites in the U.S. this month. At this time of the year, seasonal infuenza A should be well on its way down approaching low levels. Therefore, to see sharp increases raises concern that the influenza A being detected is A(H5N1) avian influenza as opposed to the seasonal human influenza viruses. Unfortunately, much of the sequencing that was being done during the COVID-19 pandemic, is no longer being done. The study: Detection of hemagglutinin H5 influenza A virus sequence in municipal wastewater solids at wastewater treatment plants with increases in influenza A in spring, 2024 | medRxiv provides us with insights. For this study, the investigators developed a PCR test to identify the H5 protein of avian influenza. They then took samples of wastewater from the time of the increases in influenza A from three of these facilities, and all three were positive for H5 and the test positivity correlated with the rise in the recent wastewater influenza A surges. The plants were located in a state with confirmed outbreaks of highly pathogenic avian influenza, H5N1 clade 2.3.4.4b, in dairy cattle. Concentrations of the H5 gene approached overall influenza A virus gene concentrations, suggesting a large fraction of the influenza A detected were H5 subtypes. At two of the wastewater plants, industrial discharges containing animal waste, including milk byproducts, were permitted to discharge into sewers.

I am going to end Part III of this update with a summary of key points from an excellent article: “A comprehensive review of highly pathogenic avian influenza (HPAI) H5N1: An imminent threat at doorstep.” https://www.sciencedirect.com/science/article/pii/S1477893923000984

1. In the recent past, the world has identified HPAI transmission involving three strains: H5N1, H5N8 and H7N9. Of these three, H5N1 is considered to be the most pathogenic, with a high mortality rate in chickens (as is required for an influenza virus to be considered highly pathogenic), but also in humans.
2. The first identified outbreak of H5N1 was among poultry in Scotland in 1959. The first known transmission of this virus to a human was in 1997 in Hong Kong. In that year, a total of 18 persons were infected, and six of them died- i.e., a case fatality rate of 33%.
3. The first recognized transmission of the virus to non-human mammals was in 2021 to foxes. However, from late 2021 on, there have been concerning spread of the virus to an ever-expanding range of animal species and increasing numbers of infections within those species. Unfortunately, the wider geographic range of infections and the involvement of new species create opportunities for the emergence of new and potentially more dangerous variants of the virus. Further, the easy transmission observed between certain mammalian species, such as Spanish minks and Peruvian sea lions, raises concern about the potential for the virus to establish reservoirs in different animal populations and pose ongoing risks to both animal and human health
4. Influenza A viruses are carried by wild birds in their intestinal tract and can be shed by these birds through various means, such as saliva, feces and nasal secretions. Transmission of HPAI H5N1 resulting in human infection primarily occurs through direct contact with infected birds.  
5. HPAI H5N1 is not efficiently transmitted to humans, however, if a pregnant woman is infected, the virus can cross the placental barrier to infect the fetus.
6. The current outbreak has seen a higher number of bird and mammal species being infected compared to previous outbreaks. This expanded range of hosts increases the potential for the virus to persist, evolve, and potentially cross species barriers, posing a threat to both animal and human health.
7. The incubation period is short, averaging 2 – 5 days.
8. In humans, as well as what has been observed in many of the mammalian species infected, after respiratory tract illness, neurologic involvement and manifestations are most common. In one study: “Out of 57 live mammals found to be infected, 53 had neurological symptoms, such as seizures, problems with balance, tremors and a lack of fear of people.” Bird flu may be making foxes and other animals behave in unusual ways | New Scientist (archive.ph)
9. In humans, severe disease results in hospitalization with complications such as adult respiratory distress syndrome (ARDS), respiratory failure, kidney failure, and an exaggerated immune response with elevated cytokines and chemokines resembling cytokine storm.

Part IV of this update is coming soon.