Avian influenza could become a human pandemic. How are countries preparing?

Joseph Giambrone, professor emeritus in the Auburn University College of Agriculture’s Department of Poultry Science with a joint appointment in the College of Veterinary Medicine’s Department of Pathobiology, has penned this article about avian influenza being a potential pandemic for humans.

The highly pathogenic avian influenza H5N1 “Bird Flu” virus is a highly contagious infection of many animal species, including humans. The virus is genetically unstable and is spread worldwide by free flying waterfowl. The virus has wreaked havoc on both domestic and wild avian populations since its emergence in 2014, leading to the loss of nearly a billion commercial poultry. U.S. wild-bird infections ballooned from 98 in the 2014-15 outbreak to 7,144 wild birds in the latest outbreak. Species like gulls, eagles, hawks, buzzards and terns were among the wild birds killed. The virus has also appeared in a variety of mammals, including dogs, cats, rodents, coyotes, swine, raccoons, squirrels, foxes, bears, dolphins, seals, whales, elephants and humans.

H5N1 virus detected for first time in dairy cattle

The H5N1 has been detected in 190 daily cattle farms and four farm workers in 14 states across the United States and in eight poultry workers in one commercial poultry company since March. Researchers say many more cases in cows and people have probably gone undetected, because farmers are reluctant to test because they did not believe the virus is a serious concern or government incentives to test did not offset their expected losses. The virus is spreading between cows through contaminated milking equipment.

The biggest risk is that the virus could evolve to infect mammals more effectively, including through the respiratory system, which would make it more difficult to contain. Given the close and regular contact that cows have with people, airborne transmission could spark a pandemic. The U.S. Department of Agriculture (USDA) tests raw milk from individual cows and wastewater to identify the virus in herds. The Food and Drug Administration has separately tested commercial milk supplies and says pasteurization kills the virus, so milk is safe to drink. It appears that older cows in mid-to-late lactation are most affected. The disease peaks in four to six days after onset and subsides within 10 to 14 days. The virus was detected not only in milk, but also in various tissues, with a notable tropism for the mammary gland's epithelial cells. Transmission between farms was linked to movement of live lactating cows, yet within-farm spread to resident cows was observed within days or weeks following movement without a clear pattern of transmission consistent on all farms.

The good news is that researchers have shown that the virus in raw milk can be inactivated by pasteurization. The recent infection in humans has mainly been a typical flu like illness. However, since 2009, 3,500 individuals have been infected with the H5N1 virus contracted from poultry with a 50% mortality rate. 

In an Aug. 16 letter addressed to the USDA Secretary of Agriculture, United Egg Producers, the National Turkey Federation and the National Milk Producers Federation requested the USDA to adopt “a sense of urgency and preparedness” to support vaccination of dairy cows, turkeys and egg laying hens. In the joint request, the industry associations outlined the economic losses associated with H5N1 influenza experienced by producers, the public sector and ultimately by consumers.

Human cases on the rise

Since late 2023, there has been a rise in human cases and the virus spreading to new animal species. The emergence of novel H5N1 strains, which are more easily transmissible, increases the pandemic threat. Immediate, coordinated preventive measures are essential. A human case of H5N1 avian influenza has been confirmed in Missouri, but unlike other cases, the patient had no known contact with animals. The United Nations (UN) detected 13 cases of bird flu in Cambodia, along with cases in China and Vietnam. According to a UN press release, “the Greater Mekong subregion, Indonesia and the Philippines are facing heightened scrutiny due to their diverse ecological landscape and limited biosecurity measures, while India, Nepal and Bangladesh are also battling outbreaks.”

Whole viral genome sequencing from cows on the affected dairy farms revealed a complex pattern of interspecies transmission, indicating the virus’ ability to jump species barriers. The study also found evidence of efficient transmission among cattle, with the virus spreading to different states after the transportation of seemingly healthy cows from an affected farm. This finding highlights the potential for subclinical carriers to spread the virus, a significant concern for disease control efforts. In non-clinical animals, viral RNA was detected in six out of 19 nasal swabs and four out of eight urine samples, indicating subclinical infection.

The current study adds to this list by reporting the first known spillover into ruminants, specifically dairy cattle. The research identifies a new reassortment genotype of the virus, which combines genetic segments from Eurasian wild bird and American bird lineages. Phylogenomic analysis revealed that the virus strains from the affected farms are closely related, suggesting potential transmission routes between farms and interspecies transmissions, including from cattle to cats and raccoons.

In July, the Global Initiative on Sharing All Influenza Data (GISAID) database released the genetic sequence of the H5N1 viruses that recently infected one of the dairy farm workers in Colorado. Notably, GISAID said that a “mammalian adaptation marker (E627K) was noted in one of the farm workers.” It is possible that cattle are shedding a mammalian-adapted virus that could be reintroduced to commercial poultry, or that selection pressures are driving the virus towards mammalian adaptation. In either case, the ongoing outbreak among cattle increases the risk that H5N1 will gain the ability to spread efficiently among humans.

Potential spread to humans, possible solutions

As cases of the H5N1 influenza continue to rise in cattle in the United States, countries are preparing for the possibility that the virus could start spreading in people. Many nations are ramping up surveillance, as well as purchasing vaccines or developing new ones. To that end, there are efforts to prepare for that possibility that include risk assessments, modelling and outbreak predictions. A risk assessment model published by the Centers for Disease Control and Prevention (CDC) indicates that this virus has a “moderate” chance of causing a pandemic. However, as stated before, this risk assessment could change if the virus continues to mutate.

A key focus of pandemic preparedness efforts is vaccines, which would protect people from getting ill should the virus spread more widely. Vaccinating people would also reduce the risk of H5N1 mixing with seasonal influenza viruses that are already well-adapted to spread in humans. Last month, the European Commission purchased roughly 700,000 doses of a flu vaccine manufactured by CSL Seqirus, in Maidenhead, UK, with the option to buy another 40 million. The vaccine protects against H5 strains of influenza A. The vaccine is given in two doses two weeks apart for individuals 18 years or older. Also in June, Finland began vaccinating people against avian influenza, focusing on high-risk workers at fur and poultry farms.

Other countries, especially the United States, should also consider vaccinating high-risk workers. In May, the U.S. Department of Health and Human Services (HHS) purchased five million more doses of the CSL Seqirus influenza vaccine for its stockpile. Researchers have recently developed an H5 mRNA vaccine candidate that has shown promise in ferrets. Last week, the HHS announced it had provided the pharmaceutical company Moderna, based in Cambridge, Massachusetts, with $176 million to develop an mRNA-based vaccine against H5 influenza.

To stay ahead of the virus, countries also are tracking its spread through increased testing of people and animals. Before the U.S. outbreak, researchers didn’t think cattle could be infected with avian influenza. They are now scrambling to develop tests specific to this virus. Alveo Technologies has recently noted that its avian influenza rapid, hand-held test panel can detect H5N1 from human infections and infected cattle.

Researchers also are monitoring sequences of the virus’ genome for changes that would improve its ability to infect cells found in the upper airways. These mutations would increase the risk to people. That being said, countries are much better prepared for pandemics due to improved medical infrastructure, the ability to rapidly isolate viruses and share the results of whole virus genome sequencing and the ability to develop and test antiviral drugs and molecular vaccines.

In addition to these scientific studies, researchers, medical experts and government authorities should properly inform the public of the current situation before panic and misinformation flood social media, as was apparent with the recent COVID-19 pandemic.