After having gone 9 years without reporting a human infection, Cambodia has reported 4 since last January.
While we'll have to wait to see if this uptick continues, across Europe, Asia, and the Americas the big concern is a newer clade 2.3.4.4b H5 virus, which has spread rapidly over the past couple of years, and has demonstrated an enhanced ability to spill over into mammalian species (see graphic at top of blog).
Human infections, however, still remain rare. But as the virus hones its abilities to infect mammals, that could change.
While one-off spillovers in the wild are unlikely to result in the creation of a new, more mammalian-adapted virus, the risks go up when the virus is introduced into a large population of susceptible hosts, allowing long chains of infection to occur. Some of the higher risk mammalian hosts include:
Previously we've seen warnings about mink (see PNAS: Mink Farming Poses Risks for Future Viral Pandemics) and swine (see Netherlands: Zoonoses Experts Council (DB-Z) Risk Assessment & Warning of Swine As `Mixing Vessels' For Avian Flu), although there are plenty of other possibilities.
Recently Denmark's SSI and Dansk Veterinaer Konsortium published an updated 32-page risk assessment on the potential spillover to mammals and subsequent adaptation to humans of the H5N1 virus.
As with other assessments we've seen, due to the unpredictable nature of influenza, they cite a low level of confidence in most of their findings. While they address a wide range of potential host species (see chart below), this report dedicates much of their attention to swine.
HPAI H5 has only occasionally been detected in swine (see here, here, here, and here), but further adaptation would be problematic given their physiology is remarkably close to humans (if that bothers you, think how the pig feels).
The authors write:
As described earlier, AIV must go through a series of changes in order to be able to infect mammals and this also applies to pigs. Although it is not entirely clear which specific mutations are necessary for adaptation to pigs, some of the mutations thought to be important are identical to the mutations which increases the risk of infection to and between people (25). Despite the fact that avH1N1 has been circulating in pigs since 1979 and has adapted to pigs (26), very few human infections with this virus have been identified. This indicates that adaptation to pigs is not necessarily sufficient for increased risk of infection to humans.
However, the assessment is that if there are changes in the virus that increase the adaptation of AIV to pigs, it will, all things being equal, increase the risk of infection of humans. Infection of pigs with AIV can also lead to the formation of new viruses that are a mixture of AIV and current circulating swine influenza viruses, including human seasonal influenza viruses that have infected pigs (18, 27). This is especially a risk in countries like Denmark, which have a high prevalence of swine flu virus positive herds.
Due to its length, I've only posted some (translated) excerpts below. Those interested can download the full document, run it through a translator, and read it in its entirety.
March 2023, updated September 2023
Update September 2023
During the summer of 2023, HPAIV H5N1 was detected in cats in Poland. The status as of 8 August 2023 is that 35 cats, one caracal (desert lynx) and one dog have tested positive for HPAI H5N1. Both outdoor cats and cats kept indoors were infected. The cats were from different areas in Poland and became ill between 15 June 2023 and 25 July 2023 inclusive (7).
High levels of HPAIV H5 virus were detected in one package of chicken meat purchased from one of the households that had sick cats. This finding may indicate that the cat in the household in question is infected via food, but it is not confirmed that the cats were infected with HPAIV. The origin of the virus detected in the feed is not known, and contamination after slaughter cannot therefore be ruled out (7). Genetic studies of virus from 21 of the cats and virus detected in the purchased chicken meat were next to identical, indicating that there was a common source of infection and that they were not infected directly from wild birds. No humans have tested positive in connection with the infected cats.
The outbreak among cats in Poland is considered to be a local outbreak, most likely due to consumption of untreated chicken meat containing relatively large amounts of H5 HPAI virus. The risk of Danish chicken meat containing the HPAI virus is still assessed to be extremely unlikely (0.001-0.1%) to very unlikely (0.1-1%).
The certainty of these estimates is assessed to be low. The Polish outbreak has thus not changed the overall risk assessments regarding infection of cats and dogs, as well as the risk of transmission to humans.
(SNIP)4. DiscussionDK-VET has assessed the risk of mammals being infected with HPAI in Denmark based on the current epidemiological situation and current knowledge. The scientific basis for the assessments is partly based on epidemiological data and partly on the results of research projects. The epidemiological data include reports from global detections and outbreaks of HPAIV in mammals and humans, as well as results from surveillance programs and individual screenings. The research data includes experimental exposure tests in different animal species with different virus variants (in vivo), laboratory tests in cells (in vitro) as well as molecular biological and bioinformatics studies of HPAIV (in silico).As shown in table 2, the certainty of most assessments is considered low, which is partly due to uncertainties related to the epidemiological and experimental data, partly to the fact that the situation is constantly changing, because viruses change genetically and outbreaks in new birds are reported - and mammal populations. The uncertainty of using epidemiological data from other areas as a basis for the assessment is due to the fact that there is a difference in how livestock are kept in different areas, including how much contact there is between different animal species and between animals and people.Another major uncertainty in using epidemiological data is that there is generally insufficient monitoring of influenza A virus occurrence in both mammals and humans globally, which most likely means underreporting of cases of HPAIV infections in mammals and the number of human infections with influenza A virus from animals in general.The high degree of uncertainty in the assessments is also due to a lack of understanding of which genetic changes in HPAIV lead to an increased risk of HPAIV infection to and between mammals and humans. There some specific mutations have been identified that are considered to be important both for HPAIV's ability to replicate in humans and mammals (mutations in e.g. the polymerase genes) and for being able to infect between mammals and humans (changes in receptor specificity in HA and the NA genes), but the precise mechanisms are still insufficiently elucidated (9). Furthermore, very little data is available for many animal species.
(SNIP)
Of the mammals that are included, DK-VET estimates that pigs pose the greatest risk of HPAIV infection, which can subsequently lead to infection and, ultimately, infection between people in Denmark. This is because pigs are susceptible to influenza viruses in general, that adaptation of HPAIV to pigs is supposed to increase the risk of infection in humans, and that Denmark has a relatively large population of pigs.
However, DK-VET estimates that the probability of infection with HPAIV for Danish pigs is between not likely (1-10%) to very unlikely (0.1-1%) in outdoor production and very unlikely (0.1-1% ) to extremely unlikely (0.001-0.1%) in conventional production and that the risk of transmission from HPAI-infected pigs to humans is low to moderate. More than 98% of Danish pigs are kept under conditions where there is very limited direct and indirect contact with wild birds, which means that the risk of introduction of HPAIV is greatly reduced.
If HPAIV is introduced, the risk of infection between pigs and the possible development of adapted variants is, however, greater in this form of production, as conventional pigs are housed in large groups, which increases the risk of spread and possible mixing with circulating swine influenza virus, which is widespread in the Danish herds. Organic pigs and free-range pigs have an increased risk of exposure to HPAIV, but on the other hand, the risk of further spread of the virus is lower, as they are housed outdoors in smaller groups.
While the words `uncertain' and `uncertainty' crop up often in this report, in fairness this group is being asked to predict the unpredictable. Anything we say about HPAI H5N1 clade 2.3.4.4b today could change overnight, with just one game-changing reassortment event (in a bird, a mammal, or a human).
How viruses shuffle their genes (reassort)
All we can say with any confidence is that HPAI H5Nx continues to evolve and we need to be prepared for surprises.
