Is the world prepared for a potential H5N1 bird flu pandemic?

High Pathogenic Avian Influenza (HPAI) infections in mammals are on the rise and 2024 could see the highest number of mammalian outbreaks ever, with 120+ outbreaks already recorded, compared to the 175 documented for all of 2023. North America accounts for a disproportionate amount of these cases, with avian influenza A (H5N1) clade 2.3.4.4b being the current variant of concern.

HPAI H5N1, was first confirmed in cattle in the U.S. on 25 March 2024, identified from samples of unpasteurised milk from sick cattle. Now confirmed in at least two humans, some key opinion leaders are now suggesting the virus may be even more widespread than what is being reported and could even be endemic in the US dairy cow population. New results from a recent pre-print have demonstrated these outbreaks possess a high zoonotic risk as cattle might be a ‘mixing vessel’ species, due to them expressing both avian and human types of influenza A receptors in their mammary gland.

Phylogenetic analysis indicates that cow-to-cow transmission was likely undetected for months since the initial spillover event at the end of 2023. While the threat to the general public remains low, the impact on humans is not only unclear but likely to be underestimated.

The response: is enough being done to prevent further spread? 

Roughly a month after it was first confirmed, the USDA implemented mandatory testing of dairy cattle prior to interstate movement in an effort to contain transmission. More recently, U.S. government officials announced they are temporarily relaxing the guidelines on how H5N1 samples are handled, stored, and transported in order to speed up the testing process.

In a further effort to curb the spread, $200m has been committed by the Biden administration which will be shared among the FDA, the U.S. CDC, and dairy farms themselves to improve prevention, testing and surveillance capabilities.

The CDC is also introducing new influenza A wastewater surveillance to aid detection efforts, collecting and testing from 600 wastewater treatment sites across the United States. Despite not exclusively looking at H5N1, the new wastewater dashboard can provide valuable insight into disease patterns and spread. However, there are limitations, for example, this method is unable to detect the source of genetic materials. 

Airfinity Senior Analyst Marco Gallotta presented live at the World Vaccine Congress 2024 on the use of wastewater data as pathogen surveillance. To request this analysis, email us at infectiousdiseases@airfinity.com. 

Worst case scenario: are we ready?

If human-to-human transmission was to occur, the U.S. may need to vaccinate over 100 million essential workers, according to Airfinity’s independent analysis. 

The good news is that there are several pandemic influenza vaccine options in various stages of the manufacturing pipeline. As of May 27th 2024, there are 78 pandemic influenza vaccines, including 44 that have been licensed whilst two vaccines are in phase II/III. Of those vaccines, 31 of them specifically target highly pathogenic avian influenza (HPAI) H5N1. The approved vaccine candidates are either inactivated or live attenuated vaccines and would be the first to be implemented in the event of a pandemic. 

In the U.S. specifically, three vaccine candidates have been approved from CSL Seqirus, Sanofi and ID Biomedical Corporation of Quebec. 

The bad news is that the currently licensed H5N1 vaccines might not be as effective against the currently circulating strains. This is because they were developed on the basis of older H5N1 strains identified in human outbreaks in Asia in the 2000s. 

Genomic analysis reveals that circulating H5N1 strains in recent years are genetically distinct from strains used in the development of approved vaccines. Therefore, there is a distinct need to evaluate the efficacy of licensed vaccines against strains from the currently circulating 2.3.4.4b clade, or shift efforts to developing new vaccines. 

Airfinity has identified three possible transmission scenarios and quantified the different factors that might affect the roll-out of a vaccination and/or treatment campaign. To request this analysis, and learn more about our simulation-based modelling for H5N1 and other pathogens, email us at infectiousdiseases@airfinity.com.