The Dangers of Zoonotic Diseases

According to a recent study published in Nature, mice and ferrets infected in a high-containment laboratory setting died from a highly pathogenic avian influenza (HPAI) H5N1 virus that was isolated from the eye of a farm worker who contracted the virus from contact with dairy cows.

Researchers also discovered that the virus isolated from the worker, who had conjunctivitis, a mild corneal inflammation, could spread through the air between ferrets that were separated and may be able to attach to and multiply in human respiratory tract cells.

The huTX37-H5N1 virus that was isolated from the worker possesses a mutation (PB2-E627K) that is commonly observed in avian influenza viruses that replicate in mammals, usually increasing the efficiency of virus replication. These mutations highlight the necessity of ongoing observation and assessment of the current H5N1 outbreak’s viruses.

The study also demonstrated that a bovine H5N1 virus is susceptible to the neuraminidase inhibitor zanamivir and the antiviral medications favipiravir and baloxavir marboxil (marketed under the brand name Xofluza) of the polymerase inhibitor class. Oseltamivir (Tamiflu), another neuraminidase inhibitor, lessens the virus’s sensitivity.

HuTX37-H5N1 multiplied in human lung and cornea cells in lab tests. In mice, the researchers found that the lethal dose of huTX37-H5N1 was less than 1 plaque-forming unit (PFU), while the lethal dose of a bovine H5N1 virus isolated from a lactating cow's milk was 31.6 PFU. Additionally, the huTX37-H5N1 virus infected all 15 mouse tissues that were tested; respiratory tissues had the highest virus levels.

Ferrets were also given a high dose of huTX37-H5N1 by the researchers. Compared to mice, ferret flu infections are more like human flu infections. The huTX37-H5N1 virus was detected in all tissues sampled, with high concentrations in the respiratory system, and all infected ferrets died within five days. The researchers used a bovine H5N1 virus to infect ferrets in a previous study, and while the disease was severe, the lethality was low.

The researchers put healthy ferrets in cages approximately 5 centimeters away from ferrets that had been infected with one of four lowering doses of huTX37-H5N1 a day prior in order to assess respiratory transmission.

Depending on the exposure dose, between 17% and 33% of the surrounding animals contracted the disease through respiratory droplet transmission, and all ferrets that were directly infected perished within 6 days. These findings suggest that, albeit inefficiently, a bovine HPAI H5 virus isolated from an infected individual can spread among mammals through respiratory droplets.

The authors point out that the person infected with the huTX37-H5N1 virus did not develop a severe illness. In fact, most human cases reported during the current outbreak have had conjunctivitis and/or mild respiratory symptoms. According to the researchers, eye infection with a low dose of bovine H5N1 virus could result in localized conjunctivitis without severe disease in humans.

Multiple exposures to seasonal human influenza viruses, they say, may provide people with low levels of protection against currently circulating HPAI H5N1 viruses—but more research is needed.

In conclusion, this study describes the huTX37-H5N1 isolate and concludes that it is pathogenic in mice and ferrets, has the potential to replicate in human respiratory tract cells, and can spread through the respiratory system in ferrets.

The authors noted that “based on these observations, every effort should be made to contain HPAI H5N1 outbreaks in dairy cattle to limit the possibility of further human infections.”