Monday, March 13, 2023

Preprint: Pathology Of HPAI H5N1 clade in Wild Terrestrial Mammals in the United States in 2022

Photo Credit USDA 


Although it undoubtedly represents only a small fraction of the actual number of mammals infected, to date the USDA lists 144 terrestrial and marine mammals in the United States that have tested positive for HPAI H5N1. 

Many mammals die in remote and difficult to access places, and are never discovered or tested, and some states appear to be more proactive in investigating outbreaks than others. 

Peridomestic mammals, like red foxes and skunks, are the most commonly reported terrestrial mammals infected, although we are seeing an increasing number of big cats and bears being infected in recent months.  

Of concern, many have been reported to be suffering from severe neurological symptoms, something we've explored previously in:

Emerging Microbes & Inf.: Neurotropic HPAI H5N1 Viruses with Mammalian Adaptive Mutations in Free-living Mesocarnivores in Canada

Pathogens: Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species

ASM J.: HPAI H5N1 Virus Infections in Wild Red Foxes (Vulpes vulpes) Show Neurotropism and Adaptive Virus Mutations

PrePrint: HPAI H5N1 Infections in Wild Red Foxes Show Neurotropism and Adaptive Virus Mutations

Today we have a preprint that looks at a large subset (n= 67) of the North American terrestrial mammals that have been identified as infected with avian H5N1, and once again we see the vast majority of these cases presented with either severe neurological manifestations, or showed signs of necrotizing meningoencephalitis during necropsy. 

As we've discussed previously, HPAI H5N1 has diversified into multiple genotypes (via reassortment) since its introduction into North America in late 2021 (see Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America).  In this study, 9 different genotypes were identified across 48 mammalian infections. 

Earlier today we saw the ECDC/EFSA report that they have identified 60 different genotypes of H5N1 within Europe since October of 2020.  HPAI H5 continues to reinvent itself at an impressive rate. 

The full 22-page report is a huge collaborative effort by more than 2 dozen researchers from nearly as many institutions, and is well worth reading in its entirety. Below you'll find the abstract, and a few excerpts, but you'll want to follow the link for the full report. 

Pathology of natural infection with highly pathogenic avian influenza virus (H5N1) clade in wild terrestrial mammals in the United States in 2022
Elizabeth J Elsmo, Arno Wunschmann, eKimberlee B Beckmen, Liam B Broughton-Neiswanger, Elizabeth L Buckles, Jayne Ellis, Scott D Fitzgerald,Robert Gerlach, Shawna Hawkins, Hon Ip, Julia Lankton, Erin M Lemley, Julianna Lenoch, Mary L Killian, Kristina Lantz, Lindsey Long, Roger Maes, Marta Mainenti, Julie Melotti, Megan E Moriarty, Shotaro Nakagun, Rachel M Ruden, Valerie Shearn-Bochsler, Danielle Thompson, Mia Kim Torchetti, Arnaud J Van Wettere, Annabel G Wise, Ailam Lim

This article is a preprint and has not been certified by peer review [what does this mean?].
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This article describes the first detections of disease due to natural infection with highly pathogenic avian influenza virus (HPAIv) H5N1 of the Eurasian lineage goose/Guangdong clade in wild terrestrial mammals throughout the United States during 2021-2022. Affected mammalian species include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). 

Infected mammals primarily exhibited neurological signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.



Since October 2021, outbreaks of highly pathogenic avian influenza (HPAI) H5N1 belonging to Eurasian lineage, clade have been reported throughout European countries (1). Highly pathogenic avian influenza virus (HPAIv) with high genetic similarity to Eurasian lineage goose/Guangdong H5 clade was first detected in the United States in December 2021 through wild bird surveillance and has subsequently spread throughout the continental United States in both wild birds and domestic poultry (2,3,4). 

In addition to causing disease outbreaks in domestic poultry, currently circulating H5N1 HPAIv appears to be persisting in wild bird reservoirs, with multiple reports of spillover into and clinical infection in various mammalian species, including red fox (Vulpes vulpes), Eurasian river otter (Lutra lutra), Eurasian lynx (Lynx lynx), ferret (Mustela putorius furo), European polecat (Mustela putorius), and stone marten (Martes foina) in European countries in 2021 (1,5). 

This case series reports on the epidemiology and pathology of natural infections with H5N1 HPAIv in terrestrial wild mammals in the United States concurrent with high levels of circulating HPAIv in wild birds and domestic poultry in 2022.



These cases represent the first detections of the currently circulating highly pathogenic avian influenza virus Eurasian lineage H5 clade in wild terrestrial mammals in the United States. Our findings build on prior reports of natural infections with this HPAIv strain in wild red foxes from the Netherlands in 2021 (13) and add to the global list of mammalian species susceptible to H5N1 HPAIv (14).

Additionally, these cases represent the first reports of natural H5N1 HPAIv infection in wild bobcats, coyotes, grey foxes, fishers, raccoons, striped skunks, and Virginia opossums. Given the broad scope and ongoing nature of the outbreak, these cases likely represent only a small percentage of the total number and species of mammals infected with the currently circulating strain of HPAIv in the United States. 


In conclusion, we demonstrate that multiple North American wild terrestrial mammal species are susceptible to natural infection with H5N1 HPAIv of Eurasian lineage goose/Guangdong H5 subtype, likely via ingestion of infected wild birds. Neurological signs were the primary clinical manifestation in these mammals, and HPAIv infection warrants consideration as a differential diagnosis along with more common causes of neurologic disease in wild mammals, such as rabies virus, canine distemper virus, canine adenovirus, and toxoplasmosis. 

Given the ongoing nature of the current HPAI outbreak, surveillance for HPAIv in wild mammals that share the landscape with or consume wild birds would contribute to a better understanding of the distribution of these viruses in free-ranging wildlife.

         (Continue . . . )

While HPAI H5 has yet to find the right combination of amino acid changes to allow it to spread efficiently in humans - and hopefully it never will - it continues to roll the genetic dice as it spreads globally, and occasionally spills over into non-avian hosts.  

While there may be some insurmountable species barrier that protects us, given the stakes, it isn't something we should be counting on.