Progression of the outbreak in sea lions, by date and country.
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The rapid spread of HPAI H5N1 down the length of South America - which began in the fall of 2022 - brought with it reports of massive die offs of wild birds (see Euronews - Peru | Tens of thousands of seabirds have died from bird flu), along with spillovers into marine mammals (see EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)).Although we've long known that marine mammals (seals, whales, sea lions, otters, etc.) are susceptible to influenza viruses (see UK: HAIRS Risk Assessment On Avian Flu In Seals) - we've never seen anything quite like the losses due to HPAI H5 over the past 18 months in South America.
While the full impact of this marine die off is unknown (many animals may have died at sea, or on remote, unsurveyed beaches), the number is at least several tens of thousands.
Along the way we've seen indications that as HPAI H5 has spilled over into marine mammals, it has acquired a number mammalian host adaptations; small amino acid changes that make it more suitable for carriage in non-avian species.
In last November's EID Journal: Highly Pathogenic Avian Influenza A(H5N1) from Wild Birds, Poultry, and Mammals, Peru, the authors cited:
2 mutations in the polymerase basic 2 protein (Q591K and D701N) associated with mammal adaptation were identified only in sequences from sea lions in Peru and from 1 human case in Chile.The $64 question - still unanswered - is how this virus is managing to spread so devastatingly among marine mammals around the world.
Since there are several plausible routes of transmission (e.g. consumption of infected birds, `high environmental load' of the virus, etc.), mammal-to-mammal transmission - while considered a possibility - can be difficult to prove.
Given the rapid and widespread dissemination of the viruses among pinnipeds in South America and the substantial associated mortalities (3,9), it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region.
Although still unproven (see EFSA Report On H5N1 in Mammals), we have another study, published last week in Travel Medicine & Infectious Diseases, that looks at the devastating impact of HPAI H5N1 on the sea lion population of South America, and considers the possibility of direct transmission between marine mammals.
Pablo I. Plaza a, Víctor Gamarra-Toledo a b, Juan Rodríguez Euguí c, Natalia Rosciano a, Sergio A. Lambertucci aShow more
https://doi.org/10.1016/j.tmaid.2024.102712Get rights and content
Abstract
We describe the evolution of the outbreak of Highly Pathogenic Avian Influenza (HPAI) A(H5N1) in sea lions (Otaria flavescens) of South America. At least 24,000 sea lions died in Peru, Chile, Argentina, Uruguay, and Brazil between January–October 2023. The most plausible route of infection is cohabiting with or foraging on infected birds. However, we urge a detailed evaluation of the sea lions actual source of infection given that the concomitant massive wild bird mortalities registered in the Pacific Ocean did not occur in the Atlantic Ocean.1. The arrival of H5N1 in South America
The (HPAI) A(H5N1) virus was detected in birds for the first time in South America, initially in October 2022 in Colombia and then in November in Peru [2,6,10]. Phylogenetic analysis suggests that the virus reached South America through multiple introductions from North America, especially along the Pacific Migratory Pathway [9,10]. The H5N1 virus arrived at the end of 2021 in North America, where high mortalities (hundreds of individuals) were reported in at least 10 wild bird species; more than 20 species of wild mammals were also affected by this pathogen in this region [3,4].
After the introductions of (HPAI) A(H5N1) into Colombia and Peru, the virus spread between birds throughout South America in a short period of time (e.g., Venezuela and Ecuador in November 2022, Chile in December 2022, Bolivia in January 2023, Argentina and Uruguay in February 2023 and Brazil in May 2023) [6]. In South America, particularly in Peru, the H5N1 virus produced alarming mortality levels in poultry, wild birds, but also in marine mammals [5,6,11]. For instance, more than 100,000 wild birds were reported to have been killed by this pathogen in Peruvian protected areas alone [11].
2. Unusual mortality of sea lionsIn January 2023, concomitantly with the deaths of wild birds and poultry due to H5N1, several dead or dying sea lions were detected on Peruvian beaches [5] (Fig. 1A and B). The clinical signs in dying individuals were mainly neurological (e.g., convulsions and tremors) and respiratory (e.g., dyspnea, tachypnea), including pathological lesions compatible with encephalitis and pneumonia [5]. Given the surrounding epidemiologic context, the first presumptive diagnosis was acute disease due to HPAI [5]. Laboratory analysis confirmed that HPAI A(H5N1) was the etiologic agent responsible for this mortality [9]. More than 5000 sea lions died as a result of this outbreak only in Peru during the summer of 2023 [5]. In addition, a common dolphin (Delphinus delphis) and several seabirds were reported as infected and killed by this virus [9,11].
During the massive mortality event in Peru, in January–February 2023 Chile began to report sick and dead sea lions with clinical signs compatible with HPAI [6,8] (Fig. 1A and B). The number of dead sea lions associated with the (HPAI) A(H5N1) virus in this country reached more than 14,000, plus thousands of wild birds [2,6,8]. Moreover, other mammals, such as the marine otter (Lontra felina), southern river otter (Lontra provocax), Chilean dolphin (Cephalorhynchus eutropia), and a spiny porpoise (Phocoena spinipinnis) were reported to have been infected by H5N1 in this country [2,4]. Genome sequences of the virus present in Chilean sea lions suggest that this (HPAI) A(H5N1) cluster monophyletically with the virus affecting the Peruvian populations [7]. Therefore, the Chilean outbreak could be considered an extension of the Peruvian one.
Sea lion mortality due to H5N1 started in Argentina in August 2023 (Fig. 1A); all gene segments of infected individuals showed a close relationship with sequences from Peruvian and Chilean sea lions [6,12]. Several cases were reported along the Atlantic coast in the following provinces: Tierra del Fuego, Santa Cruz, Chubut, Rio Negro and Buenos Aires [6,12] (Fig. 1A and B). Highly Pathogenic Avian Influenza H5N1 has killed at least 1300 sea lions, but this figure is preliminary, considering the outbreak may still be in progress [6]. Similar to what was observed for this species in Peru and Chile, affected individuals showed neurological signs before dying [6,12]. The first detection in Argentina (in Rio Grande, Tierra del Fuego Province, Argentina; −53.71557, −67.80045) occurred in August 2023, after Chile reported infected sea lion individuals in the vicinity at the end of June 2023 (in Puerto Williams, Tierra del Fuego, Chile; −54.927686, −67.621811) [6] (Fig. 1A and B). Then, Uruguay began reporting sea lions infected by H5N1 near Montevideo (Cerro beach) in September 2023 and lastly Brazil in Santa Catarina in October 2023 [6,13]. It would therefore be reasonable to assume that the Argentinean outbreak was a continuation of the Chilean event, and the Uruguayan and Brazilian a continuation of the Argentine one (Fig. 1); the Uruguayan and Brazilian viruses detected in sea lions, in fact, clustered with the Peruvian, and Chilean viruses [13,14].
The HPAI A(H5N1) virus traveled approximately 5000 kilometers from Peru to Tierra del Fuego (by way of the Pacific Ocean), and approximately 2800 kilometers from Tierra del Fuego to Uruguay and Brazil (by way of the Atlantic Ocean), infecting sea lions along the way. During this time, H5N1 killed approximately 5% and 12% of the Peruvian and Chilean sea lion populations, respectively [5,8]. The spread of the virus progressed from north to south in the Pacific Ocean between January 2023 and August 2023, and in the Atlantic Ocean, it has progressed very rapidly from south to north during August and October 2023 (Fig. 1). This wave of infection has already produced cases throughout almost the entire distribution range of sea lions, except in the south of the continent [6] (Fig. 1).
This region should be alert and prepared for the early detection of sea lions affected by (HPAI) A(H5N1), especially because in this geographical area there is a large population of this and similar pinniped species that are at risk, many in islands and the Antarctic continent [2]. In fact, this outbreak expansion recently affected Southern elephant seals (Mirounga leonina) in the Atlantic Ocean resulting in huge mortalities, with more than 17,000 pups died during this outbreak [6,15].
3. Epidemiologic behavior and transmissionThe most likely source of infection for sea lions in South America is associated with HPAI-infected birds: a spillover from wild birds to mammals seems to be the main cause of infection [5,9]. In fact, sea lions in Peru were in close contact with infected birds and have even been reported ingesting dead and dying birds [5].
However, it is important to consider and evaluate potential direct transmission among sea lions due to their gregarious behavior, the large number of affected individuals and the clustering of deaths in groups [5,14]. Most importantly, sea lion mortality seems not always associated with wild or domestic bird mortality (e.g., in Argentina there are no official reports of large bird mortalities on the coasts where sea lions are dying) (Table A.1(Table A.1), but this requires further research because it could be due to underreporting of cases by this country.
Under the current panzootic scenario, potential mammal-to-mammal transmission of (HPAI) A(H5N1) has already been suggested for both terrestrial and marine mammals [4]. Genetic analysis of virus samples obtained from sea lions in Peru, Chile, Argentina, Uruguay and Brazil shows several mutations that suggest a potential adaptation to mammals; the mutations PB2-Q591K and PB2-D701N were present in the viral genomes of infected sea lions of all these countries [7,9,[12], [13], [14]]. The evaluation of (HPAI) A(H5N1) as a virus that has adapted to replicate in mammalian species is key to assessing the likelihood of a future adaptation to humans, which could potentially lead to a pandemic event.
Nine months ago, in Avian Flu's New Normal: When the Extraordinary Becomes Ordinary, I wrote about the numbing effect that comes with the constant barrage of HPAI H5 reports from around the world.
Events that were nearly unthinkable two or three years ago (e.g. Repeated trans-Atlantic introduction of avian flu from Europe, the spread of HPAI H5 across the length of South America, numerous spillovers of H5 into mammalian species, and the arrival of HPAI H5 to Antarctica) have now become `the new normal'.
While it remains unknown whether avian H5 viruses have the ability to adapt well enough to humans to spark a pandemic, they continue to spread - and evolve - at a furious rate.
We underestimate them at our own peril.