Now that the danger of Covid-19 infections has been tamed, even if not completely defeated (more than 3,000 new cases notified in the last 30 days and a non-negligible number of hospitalizations), avian influenza viruses are reappearing attention of those who study the horizon of possible upcoming pandemic threats. Especially since, on March 25, 2024, federal officials from the United States Department of Agriculture announced that they had identified a highly pathogenic strain of avian influenza in some dairy cattle. An important leap of species.
Influenza viruses are great transformers due to their genome divided into 8 segments, which code for 11 proteins. During viral multiplication, the segments are reproduced in many copies to be then assembled into new viral particles. If influenza viruses of different origins are present, the segments can reassort differently from the originals and produce subtypes and new viral variants, with different characteristics. With these abilities to always produce new “formulations”, influenza viruses are able to infect many species, from fish to mammals, and to continuously modify themselves.
In particular for type A viruses, two proteins are crucial for causing infection and disease and are used to classify them into the different subtypes: hemagglutinin (indicated by the acronym H) and neuraminidase (indicated by the letter N). 16 different hemagglutinins and 9 different neuraminidases have been identified. Hemagglutinin is responsible for the adhesion of viral particles to the cell receptors of specific hosts and thus explains why each subtype is able to infect only some species. Neuraminidase, on the other hand, is an enzyme necessary to release, after their multiplication, viral particles in the infected organism. The antiviral drugs of choice (such as oseltamivir) are neuraminidase inhibitors which block the release of viral particles and therefore reduce the viral load and the contagiousness of the infected.
Only the H1, H2, H3 subtypes, paired in three of the 144 possible combinations of N1 or N2, are adapted to infect the human species and are responsible for seasonal epidemics. Up to now the situation has been so studied and consolidated that every year “forecasts” are made on the subtypes that will circulate in the following season and seasonal vaccines are formulated based on these projections. Also this year, in February the WHO recommended the new vaccine composition for the 2024/2025 season, listing the viral strains to be included in the update of the quadrivalent and trivalent formulation and the ministerial circular for protection against ‘flu from next autumn. Vaccinations induce an immune response against particular subtypes of H and N and repeated every year broaden the protection.
Although the seasonal flu situation seems to be under control, there is always a lurking risk of incursions by new variants and A viruses coming from other species, the well-known “spillover”. In fact, we still haven’t clarified where the Covid-19 pandemic originated, but the idea that an influenza virus “jumps” from one species to another no longer seems unlikely to us. We know that wild birds are the natural reservoir of avian influenza viruses, we know that many of these viruses are highly pathogenic for the animals they infect and have a high lethality; we suspect that the virus that caused the terrible “Spanish flu” had genes of avian origin.
With these elements available, and observing the continuous expansion of avian influenza, it is necessary to maintain a high level of attention and have good surveillance and response systems.
Among avian viruses, the H5N1 subtype is the one that has been identified the longest as a potential candidate for the leap from species to humans. The first cases of human infection were identified in 1997 in Hong Kong. From 2003 to November 27, 2023, a total of 882 human cases of influenza A(H5N1) infection, including 461 deaths, were reported globally from 23 countries. Almost all cases of human infection with avian influenza A(H5N1) have been classified as sporadic and linked to close contact with live or dead infected birds or environments contaminated by the virus. In 2020, a highly pathogenic bird-pathogenic H5N1 (2.3.4 4b) strain, different from those that have circulated previously, began to spread with migratory birds in many parts of Africa, Asia and Europe causing extensive bird deaths. In 2021 the same viruses passed into North America and in 2022 into South America.
The joint FAO-WHO document of 23 April 2024 reports that in the meantime the frequency of reports of infections in marine and terrestrial animals other than birds, including some mammals and domestic animals, has increased. Epidemic outbreaks have been reported in fur-bearing animals in Finland and Spain, confirming the possibility of contagion between mammals. In the United States they have found infections in goats and dairy cows and the H5N1 strain (2.3.4 4b) has been identified in the majority of cases. Finally, again in the USA, the most sensational event due to its numerousness: cases of H5N1 infections in dairy cattle belonging to 67 different farms in 9 different states and high viral concentrations (even higher than what was found in the respiratory system ) have been detected in the milk produced.
The ways in which the infection spreads among cattle have not yet been clarified, but the ability of the viruses to infect mammals is clear, demonstrating the spillover from birds to cattle. Research, not yet verified, suggests the susceptibility of cattle due to an abundant presence, in the mammary glands, of cellular receptors suitable for infection.
The good news is that it does not yet appear that viruses are capable of transmitting themselves by direct contagion from one animal to another: one of the elements necessary for triggering an epidemic even among animals is therefore missing, while it is suspected that infections have spread through mechanical contamination during milking.
For now, the public health response in the US has focused on limiting infections among cattle herds and surveillance of workers exposed to infected animals. A federal order requires that all dairy cattle be tested for H5N1 infection prior to interstate transfer and quarantined for 30 days upon arrival.
Given the lack of evidence on how cattle are infected, one of the critical points raised is the lack of clear indications on how to manage herds after quarantine. Staff working in contact with animals should be monitored to identify cases of infection, but the presence of illegal workers does not help the process. Additionally, a shortage of public health epidemiologists and a shortage of dedicated funding are cited in a CDC investigation as barriers to monitoring exposed personnel. Surveillance activities on approximately 350 people have so far identified 3 cases of infection in workers in contact with infected cattle in two different states. The clinical pictures observed for the three infected people were mild (conjunctivitis and in one case cough) and certainly would have gone unnoticed without careful surveillance.
Infection risk assessments for the general population by WHO, CDC and ECDC indicate a very low risk. The possible presence of viruses in bovine milk is eliminated by pasteurization, so there are no reasons for health alarm for people. What is happening, however, is yet another opportunity to remind us that human, animal and environmental health are inextricably linked and that only public health can implement effective surveillance and response systems, also keeping at bay useless alarmism.
