#18,209
Six months can be a long time when discussing the rapidly changing threats from emerging infectious diseases. Last January the UK's Health Security Agency released a risk assessment that reassuringly placed the HPAI H5N1 virus in a pre-pandemic level 3 category.
They wrote:
Assessment
The avian influenza outbreak in the UK is assessed as at risk level 3*. The apparent transmission between mink is of significant concern but there is no clear evidence that this has continued in mammalian species since the initial outbreak. The UK assessment is consistent with the international picture with the same or similar viruses detected in multiple regions, evidence of mammalian spillover, but very few detected human infections.
At present, there are no indicators of increasing risk to human health, however this is a low confidence assessment. The risk assessment is dynamic and requires regular review during this period of unusually high levels of transmission in birds with mammalian spillover.
Two months later we learned of the outbreak of HPAI in American cattle - and of its rapid spread across the nation - which led to a revised risk assessment from the UKHSA in May, where they stated:
Situational assessment: the outbreak is currently at level 3 (with high confidence) and may have risen to level 4 (low confidence)
Over the past 3 weeks we've seen a 4th H5 human infection linked to dairy cattle exposure, and 9 more linked to infected poultry. Considering that up until 3 months ago, the U.S. had only reported 1 (weakly positive) case, that represents a significant increase.
We've also seen recent reports suggesting `sustained and efficient' transmission of the virus - a highly specific phrase which is not used lightly - both in cattle, and to a lesser degree in marine mammals.
Yesterday the UKHSA released an updated risk assessment which raises - incrementally - their risk assessment from level 3 to level 4 (moderate confidence). The full report (including their rationale) runs 11-pages, so I've only posted some excerpts below.
Follow the link to read the full assessment. I'll have a brief postscript after the break.
Influenza A(H5N1) 2.3.4.4b B3.13: UScattle outbreak updateHuman health evidence review and situational assessment 17 JulyUKHSA, APHA, FSA, and DefraOverview
The UK Health Security Agency (UKHSA) is working with the Animal and Plant Health Agency (APHA), the Department for Environment, Food and Rural Affairs (Defra), Food Standards Agency (FSA), and the public health agencies of the 4 nations to monitor the risk to human health from emerging influenza viruses.
A previous assessment of this situation was published in May 2024.
Current evidence review
1. Animal outbreak
There is ongoing transmission of influenza A(H5N1) in the US, primarily through dairy cattle but with multispecies involvement including poultry, wild birds, other mammals (cats, rodents, wild mammals) and humans (1, 2). There is high uncertainty regarding the trajectory of the outbreak and there is no apparent reduction in transmission in response to the biosecurity measures that have been introduced to date. There is ongoing debate about whether the current outbreak should be described as sustained transmission given that transmission is likely to be facilitated by animal farming activities (3). However, given that this is a permanent context, the majority of the group considered this outbreak as sustained transmission with the associated risks.
The available genomic data show a single expanding clade, genotype B3.13, consistent with ongoing transmission through dairy cattle and spillover into other mammals and birds.
2. Human cases
There is evidence of zoonotic transmission (human cases acquired from animals). There is likely to be under-ascertainment of mild zoonotic cases (4). There have been ten human cases detected associated with the current US outbreak, 4 in dairy workers at separate farms and 6 in poultry workers exposed during a single depopulation event at which a large number of workers were symptomatic (1).
Environmental factors may have contributed to increased viral exposure at this site (5). Human case genomes where available are within the cattle outbreak clade although the first human case in Texas is distinct (3). The sequence from this case (EPI_ISL_19027114) does contain the HA L131Q and T211I mutations present in all B3.13 sequences, but not contain the PB2 M631L, PA K497R or the NA N71S mutations observed in the main cattle outbreak clade. It contains PB2 E627K and D441N mutations, K142E in PA, and S7L and Q40R in NS1 that are not observed in other B3.13 sequences.
The ongoing cattle outbreak in dairy cattle with spillover to poultry farms means that there could be large numbers of human exposures and increased opportunity for zoonotic cases. However, there are insufficient data to assess whether the rate of zoonotic infection is unusually high.
(SNIP)4. Evidence relevant to human transmissibilityDespite the increased activity of the bovine virus polymerase with the PB2 M631L and PA K497R mutations in human and other mammalian cells, the lack of human receptor binding supports the virological observations that bovine virus (EPI_ISL_19014384), like earlier clade 2.3.4.4b viruses that circulated in the UK, replicates and spreads poorly in human airway epithelium at 33°C (similar to temperatures in human nasal passage) (10). Preprint data finds respiratory inoculation is possible in experimentally infected heifers and published data suggests inefficient respiratory transmission in the ferret model (8, 16, 17).5. Characteristics of genotype B3.13There are insufficient data to assess whether the genotype B3.13 was already fitter in birds or mammals at the point of spillover (that is, had a predisposition to cause a mammalian outbreak) and therefore it is difficult to assess whether other genotypes seen in Europe could cause similar outbreaks given similar opportunity. In vitro data shows that other influenza A viruses with internal genes derived from avian viruses including those of clade 2.3.4.4b replicate efficiently in bovine cells (10). Widespread transmission in marine mammals is also noted in South America, involving a slightly different genotype (18).
With the current evidence we should not assume that the risk of a mammalian outbreak is limited to clade B.3.13.6. Risk of reassortmentThere is an ongoing elevated risk of reassortment with other influenza viruses given the range of animal and human infections occurring. There is also early in vitro data suggesting that human seasonal influenza viruses can replicate in bovine cells (10). This implies that reassortment resulting in exchange of genes between the bovine virus, avian influenza viruses and fully human adapted influenza viruses could also occur in cattle, as it does in pigs.Current situational assessmentLevels are indicators that a zoonotic influenza virus outbreak may be an increasing human health threat, either because the opportunities for it to evolve are increasing or because there is evidence that it has already begun to evolve. All levels are pre-pandemic events. The current situational assessment is shown in Table 1 alongside accompanying evidence, updated from the previously published situational assessment (May 2024).
Risk assessments are - by necessity - based on older, often fragmented, and usually rapidly changing information. As such, they are always going to be behind the curve.
They can be useful, however, since they can show changes in our levels of concern over time. And it is clear that concerns over HPAI H5 are rising around the globe.
In addition to raising the pre-pandemic level, this report also acknowledges that it isn't just the bovine B3.13 genotype - currently spreading in North America - that poses a zoonotic threat. This is a palpable shift from the UK HAIRS Risk Statement On Avian Influenza (H5N1) In Livestock released in late May.
Zoonotic threats advance and retreat, often without warning, and so we could find ourselves back at level three in the fall, still at level four, or somewhere decidedly worse.
While these risk assessments can't predict the future, they can help us decide where best to put our prevention and preparedness efforts.
Assuming, of course, that those who are in charge of such things are actually paying attention.
