Epidemiological data of an influenza A/H5N1 outbreak in elephant seals in Argentina indicates mammal-to-mammal transmission

Abstract

H5N1 high pathogenicity avian influenza virus has killed thousands of marine mammals in South America since 2022. Here we report epidemiological data and full genome characterization of clade 2.3.4.4b H5N1 HPAI viruses associated with a massive outbreak in southern elephant seals (Mirounga leonina) at Península Valdés, Argentina, in October 2023. We also report on H5N1 viruses in concurrently dead terns. Our genomic analysis shows that viruses from pinnipeds and terns in Argentina form a distinct clade with marine mammal viruses from Peru, Chile, Brazil and Uruguay. Additionally, these marine mammal clade viruses share an identical set of mammalian adaptation mutations which were also present in tern viruses. Our combined ecological and phylogenetic data support mammal-to-mammal transmission and occasional mammal-to-bird spillover and suggest multinational transmission of H5N1 viruses in mammals. We reflect that H5N1 viruses becoming more evolutionary flexible and adapting to mammals in new ways could have global consequences for wildlife, humans, and/or livestock.

Fig. 1. Mass mortality, clinical signs, and post-mortem findings of elephant seals at Punta Delgada (Península Valdés, Argentina) during an outbreak of H5N1 HPAI.

A Hundreds of elephant seal pup carcasses accumulated along the high tide line of the beach at Punta Delgada; a sea lion carcass (arrow) and patchily distributed living elephant seals (far background behind the arrow) are also visible. B Pup presenting with open mouth breathing and tremors/twitching. C Pup presenting with labored breathing and foamy nasal discharge. D, E Abundant white foam on the snout and draining from the sectioned trachea of a dead pup. F Markedly heterogeneous and congested lung surface in a dead pup. G Bloody and mucous nasal discharge in a dead subadult male.

Fig. 2. Phylodynamics of H5N1 HPAI (2.3.4.4b) viruses in South American marine mammals and birds.

A Time-scale MCC tree inferred for the concatenated genome sequences (~ 13 kb) of 236 H5N1 influenza A viruses (clade 2.3.3.4b) collected in five South American countries (Argentina, Brazil, Chile, Peru, Uruguay) and in South Georgia and the Falkland/Malvinas Islands. Branches are shaded by inferred host species (4 categories). Posterior probabilities are provided for key nodes. The same tree with tip labels and posterior probabilities for all nodes is available in Supplementary Fig. 4. B Direction of virus gene flow between locations and hosts, inferred from “Markov jump” counts across the posterior distribution of trees inferred using a Bayesian approach (values under 0.5 excluded). Different host groups are indicated with different colors: wild birds (orange), marine mammals (red) and terrestrial mammal (blue). The same graphic with 95% HPD (highest posterior density) labels is available in Supplementary Fig. 5. Tree with all location states labeled is available in Supplementary Fig. 6. C Posterior distributions of evolutionary rates (substitutions per site per year) inferred for the complete virus genome (all positions) and for only the third nucleotide position for H5N1 (2.3.4.4b) in South America, partitioned into two host categories: marine mammal clade (excluding any human and avian viruses) and avian (wild bird/poultry) clade (excluding any mammal viruses). Source data for the histogram graph are provided as a Source Data file.

Fig. 3. Mutations defining the marine mammal clade of H5N1 HPAI (2.3.4.4b) viruses.

Amino acid changes are listed for new mutations that arose in the marine mammal clade of the H5N1 HPAI (2.3.4.4b) viruses that are not observed in any other avian viruses included in this study from South America, mapped against the subsection of the MCC tree with the marine mammal clade (see Fig. 2A). Virus names and associated mutations are colored by country. A question mark indicates that no sequence data is available at that position for that virus. HA mutations refer to H5 numbering.

Fig. 4. Chronology and hypothesized pathways of spread of H5N1 HPAI (2.3.4.4b) viruses in South America, 2022–2023.

H5Nx HPAI detections (1-Sep-2022 to 31-Dec-2023) reported to the World Animal Health Information System (WAHIS/WOAH) and by the Chilean Servicio Agrícola y Ganadero (SAG) are represented by orange circles (wild birds), green triangles (domestic birds) and blue squares (mammals). Note that there are significant differences in surveillance strategies among countries that may produce gaps or distortions in the geographic distribution of H5Nx HPAI detections and the presumed pathways of virus spread. The location of the outbreak investigated in this study (Península Valdés) is highlighted in red. Arrows represent the timeline of hypothesized pathways of virus spread, as derived from the chronology of detections and our phylodynamic analysis. The pathways of virus spread and significant events of the avian and marine mammal clade viruses are represented in dark orange and dark blue, respectively. Note that virus spread pathways in this figure are intended as a conceptual model and are not geographically precise. Source data for the geographic locations of H5Nx HPAI detections are provided as a Source Data file.