#18,096
Although we are closely watching a distinct genotype (B3.13) of H5N1 clade 2.3.4.4b running rife in American dairy cattle, in South America another genetically distinct H5N1 virus is causing mass mortality in sea lions and seals.
A few of many past blogs on these events include:Unlike the American cattle genotype, this H5 virus has spread across multiple countries, killing tens of thousands of its mammalian hosts.
Travel Med. & Inf. Dis.: Pacific and Atlantic Sea Lion Mortality Caused by HPAI A(H5N1) in South America
EID Journal: HPAI A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023
EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)
Marine mammals have been long known to be susceptible to influenza A infection (see here, here, here, and here), but previous outbreaks have tended to be smaller, shorter-lived, and geographically limited.
The spread in marine mammals from Peru on the Pacific coast to southern Brazil on the Atlantic side is unprecedented, leading some researchers to suspect mammal-to-mammal transmission.
Today we've a preprint (published June 1st) that presents even more evidence suggestive of mammal-to-mammal transmission, including the identification of a marine-mammal specific clade.
The authors wrote:
Across the genome, we identified more than 64 amino acid changes in the H5N1 HPAI viruses from Península Valdés when compared viruses from birds and mammals from Argentina, other South American countries, Antarctica, North America (genotype B3.2 from 2022–2023) and the original Goose/Guangdong (Gs/Gd) (Supplementary Table 4).
Of the 64 mutations, 18 are potentially associated with increased virulence, transmission or adaptation to mammalian hosts, and fifteen are present in H5N1 viruses from Argentina’s coastal outbreaks in marine mammals and terns but absent in H5N1 (B3.2 genotype) strains from North America and from goose/poultry strains from Argentina (Supplementary Table 4). Of note, eleven of the fifteen common mutations were also present in the human case in Chile (Supplementary Table 5).
This is, as you might imagine, a lengthy (33 Pages) and at times technical report, and while I've posted some excerpts below, is well worth reading in its entirety. I'll have postscript after the break.
Massive outbreak of Influenza A H5N1 in elephant seals at Peninsula Valdes, Argentina: increased evidence for mammal-to-mammal transmission
Marcela M Uhart, Ralph E. T. Vanstreels, Martha I. Nelson, Valeria Olivera, Julieta Campagna, Victoria Zavattieri, Philippe Lemey, Claudio Campagna, Valeria Falabella, Agustina Rimondi
doi: https://doi.org/10.1101/2024.05.31.596774+
Abstract
H5N1 high pathogenicity avian influenza (HPAI) viruses of the cla(SNIP)de 2.3.4.4b have killed thousands of marine mammals in South America since 2022. In October 2023, following outbreaks in sea lions in Argentina, we recorded unprecedented mass mortality (~17,000 individuals) in southern elephant seals (Mirounga leonina) at Peninsula Valdes. +
Seal pups were disproportionately affected. Adult seals departed early, disrupting social and breeding structure. Frequent interactions with sea lions and scavenging by seagulls were observed. Deaths of terns concurred with seals but peaked weeks later. HPAI H5N1 was confirmed in seals and terns. Moreover, genomic characterization showed viruses from pinnipeds and terns in Argentina form a distinct clade with marine mammal viruses from Peru, Chile and Brazil.These mammal-clade viruses share an identical set of mammalian adaptation mutations which are notably also found in the terns. Our combined ecological and phylogenetic data support mammal-to-mammal transmission and occasional mammal-to-bird spillover.To our knowledge, this is the first multinational transmission of H5N1 viruses in mammals ever observed globally. The implication that H5N1 viruses are becoming more evolutionary flexible and adapting to mammals in new ways could have global consequences for wildlife, humans, and/or livestock.
(SNIP)
From a public health perspective, mammal-to-mammal transmission could be a critical stepping-stone in the evolutionary pathway for these viruses to become capable of human-to-human transmission and thus potentially pandemic 67. As mentioned previously, some of the mutations found in the strains of the marine mammal clade are already known to be of concern.
Specifically, the mutation D701N in PB2 has been shown to compensate for the lack of the E627K mutation in PB2 in terms of improved viral growth in mammalian cells and enhanced aerosol transmission of H3N2 and H5N1 viruses68 .
On the other hand, the phenotypic effects of mutations in other gene segments found in the H5 viruses from our study(Supplementary Table 5) are not yet known, and the possibility that some of them may also open evolutionary pathways that enhance the virulence or transmission of these viruses to mammals (including humans) cannot be ruled out.The fact that the H5N1 HPAI virus detected in a human case in Chile 69 belongs to the marine mammal clade described in this study, highlights the potential risk to public health.
Moreover, given pinniped susceptibility to multiple IAVs (including human-like strains 38–40 ), and their frequent intermingling with other avian and mammalian hosts, co-infections could occur, potentially enabling the emergence of reassorted strains 36,70 .
Hence, while there is no evidence for genomic reassortment occurring in pinnipeds at this time, the broad circulation of H5N1 HPAI viruses in marine mammals is a warning we must not ignore.
In conclusion, as recently demonstrated by the detection of HPAI H5N1 viruses in ruminants 71 , few if any compartments and species are outside the scope of the clade 2.3.4.4b strains. Thus, moving forward, HPAI management requires holistic strategies that recognize the interconnectedness of human, animal, and environmental health and safeguard biodiversity, promote sustainable practices, and enhance resilience globally to emerging infectious diseases.
Although we still don't know if H5N1 is actually capable of sparking a human pandemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the number of ongoing field experiments around the globe grows with each passing day.
And it is fair to say we are probably only vaguely aware of a fraction of them.
Even in our own backyard - after > 2 months - we still don't know how widespread genotype B3.13 is in American livestock. After more than a year, there are still no answers to the massive die off of seals in the Caspian sea, and we know very little about what is happening with H5N1 in China, Russia, and most of Africa.
Most of these field experiments will be failures. If it were easy for nature to cobble together a pandemic virus, we'd be hip deep with them all the time.
But with growing diversity, comes more opportunities for the virus to get `lucky'. And that applies not only to H5N1, but also to a panoply of other subtypes, all embarked on their own evolutionary journeys.
A few recent blogs include:
Recent Papers On The Zoonotic Potential of Bat-borne H9N2
Emerg. Microb. & Inf.: Long-term Co-circulation of Multiple Influenza A viruses in Pigs, Guangxi, China
Transboundary & Emerg. Dis.: H3 Avian Influenza Virus Isolated from China in 2021–2022 Showed the Emerging H3N8 Posed a Threat to Human Health
Viruses: Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice
“Everything you say in advance of a pandemic seems alarmist. Anything you’ve done after it starts is inadequate."- Michael Leavitt, Former Secretary of HHS
