In the wake of the Covid-19 pandemic, we're now facing a newly evolved highly pathogenic (HPAI) H5N1, also known as "bird flu." This new clade 2.3.4.4b is extremely worrisome.

A Brief History

It's important to know the history of this bird flu virus to understand what might come next. While other H5 viruses have appeared, including H5N2, H5N3, H5N6, H5N8, and H5N9, I'm only going to discuss H5N1 since it's the one causing the greatest concern now.

According to the CDC, HPAI H5N1 first appeared in a chicken outbreak in Scotland in 1959. It was identified in 1996 in farmed geese in Southern China. One year later, it was found in Hong Kong where the first zoonotic spread from chickens to humans occurred, resulting in 18 infections and 6 deaths. The Hong Kong authorities killed 1.3 million chickens and other domestic poultry in an attempt to stop the virus. The mass culling slowed but didn't stop its spread.

From 2003 to 2004, HPAI H5N1 outbreaks were reported in 9 neighboring Asian countries. Domestic ducks were suspected of being the source of these outbreaks. Unfortunately, it began spreading to humans again with cases occurring in January 2003. Three out of five family members from Hong Kong became ill after visiting the Fujian province in mainland China. The father and his 7-year-old daughter died. The 8-year-old son survived.

Over the next 10 years, HPAI H5N1 spread widely with occasional spillover events to humans. Human cases were reported in Southeast Asian countries including Thailand, Cambodia, Indonesia, Laos, and Viet Nam. Turkey, Iraq, Azerbaijan, Egypt, Djibouti, Pakistan, and Bangladesh also reported human cases.

In 2011, the UN Food and Agriculture Organization (FAO) declared that HPAI H5N1 had affected animals in 63 countries and territories across Africa, Asia, and Europe. Three years later, the first human HPAI H5N1 case was reported in the Americas. A traveler returning from China tested positive for the virus in Canada.

That same year, virologists in the Netherlands, Japan, and the US conducted gain-of-function research on HPAI H5N1 by modifying the virus so that it could easily spread between mammals (i.e., ferrets) to determine what factors made it jump species. This research was funded by the NIH and generated great concern among scientists. Public outrage was so great that it led to a funding pause. (Note: This pause ended on December 19, 2017).

From November 2003 to May 2019, a total of 861 reported human cases and 455 deaths were reported across 17 countries—an estimated mortality rate of almost 53 percent. However, the number of unreported cases were unknown. The virus evolved as it circulated among wild and domestic birds.

The Emergence of a New HPAI H5N1 Clade

A major change occurred in mid-2021 in Europe when a new viral clade 2.3.4.4b appeared after a genetic reassortment of the A/good/Guangdong/1/96 H5-lineage virus. This new viral clade spread widely and was noted for infecting across many terrestrial and marine mammal species.

In the winter and spring of 2021/2022, this new viral clade spread to the U.S., infecting wild and domestic birds, dairy cattle, and cats. The cows developed nonspecific signs of illness, but the cats died after being fed unpasteurized milk from the infected cows. The first reported human case occurred on April 1, 2024 in a dairy worker with a history of exposure to presumably infected dairy cattle in Texas. The individual developed conjunctivitis. In different countries, human infections have ranged from mild conjunctivitis to fatal pneumonia.

Clade 2.3.4.4b HPAI H5N1 has killed thousands of marine mammals in South America including a massive outbreak in southern elephant seals (Mirounga leonina) in Argentina in 2023. It has killed more than 30,000 sea lions off the coast of Chile and Peru as well as dolphins, otters, and porpoises setting off considerable concern among veterinarians.

Recently, an article in Science described a genetic and structural analysis of the HPAI H5N1 clade 2.3.4.4b.

The U.S. Response

According to the USDA, there is now a multi-state outbreak of clade 2.3.4.4b in dairy cattle and poultry. Fifty-eight people have been confirmed to have been infected. There has been no reported human-to-human spread. Nine thousand people have been monitored after being exposed to infected animals. On December 6, 2024, the USDA began a National Milk Testing Strategy to enhance farm biosafety measures.

However, there are problems.

Farmers distrust the federal government and don't want data collected from their farms. They have financial concerns if their herds or workers test positive. Inexplicably, they have been reportedly refusing to allow their workers to wear protective gear. The CDC has no legal authority to mandate these measures.

Workers might be afraid of losing their job if they test positive. Many cases in farm workers might not be getting reported.

Meanwhile, the virus continues to spread. The first case of HPAI H5N1 has been reported in pigs sharing a backyard farm in Oregon with infected poultry.

Distrust between farmers, farm workers, and public health officials does not bode well for containing this virus. There is no up-to-date vaccine for clade 2.3.4.4b for humans, and even if there were, public trust for vaccines and for public health, in general, is low. An experimental mRNA vaccine has been highly effective in preventing severe illness and death in lab animals and might be used in livestock to reduce spread to humans. Other animal vaccines are also being developed.

Options for containing spread of the virus as contagious as HPAI H5N1 clade 2.3.4.4b to humans are limited to disease surveillance, food testing, protective gear, isolation, and vaccines (if available). The antiviral drug Oseltamivir (Tamiflu) would be recommended for people with early signs of infection.

Meanwhile, Covid-19 hasn't disappeared.

The HPAI H5N1 clade 2.3.4.4b continues to spread. Wastewater surveillance for HPAI H5N1 viral RNA provides useful information and doesn't require public participation other than flushing toilets.

Understandably, the public is tired of pandemics. Public health requires good communication, transparency, honesty, trust, and cooperation. Presently, trust is very low on the part of the public. Unless trust is built, policies developed to contain the virus, potentially much more deadly than Covid-19, might be futile.