A new report has sounded the alarm on the evolution of the avian influenza virus, with comprehensive genome sequencing showing that the current strain is now capable of multidirectional infections across species. While human-to-human risk remains low, it's a worrying step towards the virus honing its transmission ability.
“This is one of the first times that we are seeing evidence of efficient and sustained mammalian-to-mammalian transmission of highly pathogenic avian influenza H5N1,” said corresponding author of the study Diego Diel, director of the Virology Laboratory at the Animal Health Diagnostic Center (AHDC) at Cornell University.
Cornell scientists have uncovered more about the 'spillover' of the highly pathogenic avian influenza (HPIA) H5N1 clade 2.3.4.4b virus, which is characterized as a "significant increase in the intensity, frequency and geographic range" of the zoonotic disease and has killed hundreds of millions of wild and farmed birds since it took hold in 2021. It's now reported in every state in the US, and every continent, except Australia and the rest of Oceania, has had outbreaks.
While it's been observed that there has been likely transmission between mammals, the Cornell scientists have delivered evidence of this, with whole genomic sequencing clearly showing that the virus has passed between mammals, and not just in one direction as with many animal pathogens and hosts. On the plus side, the lab work did not turn up any evidence of any clade 2.3.4.4b mutations that would indicate it had worked out an easy path to jump to humans.
On that note, it can and has infected humans – HPAI, since it was first recorded in China in 1996, has infected just 889 people, however, it proved fatal in 463 of those cases. Yet infection so far is limited to contact with contaminated waste or cow milk, and despite it targeting the human respiratory system, there's no evidence of airborne transmission yet.
“The concern is that potential mutations could arise that could lead adaptation to mammals, spillover into humans and potential efficient transmission in humans in the future,” said Diel.
The team analyzed viral nucleic acid taken from milk, nasal swabs, whole blood, serum, feces, urine and 608 tissue homogenate from dairy cows across nine farms in the US. What was particularly alarming in the findings was that seemingly healthy animals moved interstate were able to then pass the virus onto cattle at their new farm, indicating that containing the spread may be more difficult than previously thought.
"Our epidemiological investigation combined with genome sequence and geographical dispersal analysis provides evidence of efficient intra- and inter-species transmission of HPAI H5N1 genotype B3.13," the researchers noted. "Soon after apparently healthy lactating cattle were moved from Farm 1 to Farm 3, resident animals in Farm 3 developed clinical signs compatible with HPAI H5N1 providing evidence to suggest that non-clinical animals can spread the virus."
This is concerning, given there is no way to 'rapid test' for the virus like there is for COVID-19; like for much of the pandemic, right now the go-to method is costly and time-consuming quantitative polymerase chain reaction (qRT-PCR) testing.
"The bad news is that at present, there are currently no commercially available diagnostic tests to detect H5N1 specifically," Ayoade Alakija, Special Envoy for the Access to COVID-19 Tools Accelerator, told Al Jazeera in June. "Nucleic acid-based (molecular) tests are the current gold standard for the detection of influenza viruses, but they generally require lab infrastructure to support their use. And even when such infrastructure is available, it may not function fast enough."
In this latest study, the team looked at the whole viral genome sequence in cows, birds, domestic cats and a raccoon, and the findings suggest H5N1 can spillover in more than just one direction (say, bird to mammal). The scientists believe that the birds infected – great-tailed grackles (Quiscalus mexicanus) and rock pigeons (Columbia livia) – most likely became infected not from other avian species but through environmental contamination or aerosols in the atmosphere through milking or cleaning on the dairy farms.
The data also revealed "high tropism" of the virus – or, its ability to infect particular cells – such as the way it targets the mammary gland in dairy cows, resulting in high viral loads being shed into milk from the sick animals. (It's worth noting, though, that the pasteurization process kills 100% of the virus.)
“It is a highly pathogenic strain,” explained Erin M. Sorrell, associate professor at Johns Hopkins Bloomberg School of Public Health in Maryland. “It has the ability to replicate outside the traditional locations where low-pathogenic influenza does: the intestinal tract for poultry; the upper and lower respiratory tracts in humans. The virus becomes systemic in its infection.”
The Cornell team noted that it's critical to have ongoing monitoring of farmed animals, and the US Department of Agriculture has in place testing programs that are free to access. However, scientists across the world remain vigilant, closely monitoring for 'surprises' that have the blueprint of virus mutation.
"This remains I think an enormous concern," said Jeremy Farrar, the World Health Organization's chief scientist, in April.
In recent years the virus has spilled over into red foxes (Vulpes vulpes), bears (Ursus americanus), and harbor seals (Phoca vitulina). It has reached polar regions to infect and kill a polar bear (Ursus maritimus) in the Arctic and elephant (Mirounga leonine) and Antarctic fur (Arctocephalus gazella) seals, plus gentoo penguins (Pygoscelis papua) in Antarctica. In the US last year, two outbreaks resulted in the high mortality of harbor seals in Maine and Washington, as well as infecting numerous domestic cats and a goat (Capra hircus).
"Epidemiologic and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state," the Cornell team noted. "These results demonstrate the transmission of HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface underscoring the ability of the virus to cross species barriers."
In another new study, scientists from the University of North Carolina (UNC) at Charlotte and the Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER) have discovered that this virulent strain of H5N1 appears to be much better at circumventing antibodies in its hosts – including those of humans.
Using advanced AI and physics-based modeling techniques to assess transmission and predict future outcomes, the team found that, "the virus is evolving immune escape of our medical defenses." And because of the nature of how H5N1 has spread, with no central reservoir in a species or location, it does establish it as a real threat to evolve from epidemic to pandemic.
"H5-related avian influenza A is an emerging pathogen in humans while being an ongoing pandemic in wildlife for over two years," said White, assistant professor of Bioinformatics at UNC. "Our predictive study provides a window to the future of using AI in the arms race against emerging pathogens."
This type of research, which combines existing modeling and historic data using AI tools, is likely to be critical in keeping one step ahead of H5N1. Understanding virus protein-antibody interactions will also be crucial to developing effective vaccines if the worst case scenario emerges.
An unedited version of Cornell University research has been published in Nature, while the UNC study has been published on the bioRxiv preprint server.
Source: Cornell University, University of North Carolina at Charlotte via phys.org
