Highly pathogenic avian influenza: Unprecedented outbreaks in Canadian wildlife and domestic poultry

Abstract

Canada experienced a wave of HPAI H5N1 outbreaks in the spring of 2022 with millions of wild and farmed birds being infected. Seabird mortalities in Canada have been particularly severe on the Atlantic Coast over the summer of 2022. Over 7 million birds have been culled in Canada, and outbreaks continue to profoundly affect commercial bird farms across the world. This new H5N1 virus can and has infected multiple mammalian species, including skunks, foxes, bears, mink, seals, porpoises, sea lions, and dolphins. Viruses with mammalian adaptations such as the mutations PB2-E627K, E627V, and D701N were found in the brain of various carnivores in Europe and Canada. To date this specific clade of H5N1 virus has been identified in less than 10 humans. At the ground level, awareness should be raised among frontline practitioners most likely to encounter patients with HPAI.

Introduction

While the medical community has been focused on the SARS-CoV-2 pandemic, another virus has rapidly emerged. A highly pathogenic avian influenza (HPAI) H5N1, so named because of its effects on poultry, was detected in Europe and Africa in 2020 and rapidly spread among wild birds in Europe, Africa, and Asia in 2021 (1–3). The spectre of H5N1 has been present since it was first identified in Southern China in 1996 (4). For several years, H5N1 viruses were not widely detected; however, in 2003, H5N1 re-emerged in China to cause widespread outbreaks in poultry across Asia. In 2005, wild birds spread H5N1 to poultry in Africa, the Middle East, and Europe (4). The hemagglutinin (HA) gene of the virus has diversified into over 20 distinct HA clades and numerous reassortants have also emerged (5). Prior to 2020, the virus circulated in more than 18 countries, primarily being detected in birds and some other animals. While there has been limited human to human transmission, there were over 860 humans infected with mortality rates of approximately 50% (6).

Avian Transmission

By December 2021, the United Kingdom had reported multiple outbreaks of HPAI H5N1 clade 2.3.4.4b. It is believed, based on bird migration patterns, that birds from the North American and European flyways intermixed in Iceland, allowing the introduction of the H5N1 virus to wild birds in Newfoundland, rapidly dispersing across North America through the four major migratory bird flyways (7). Introduction of this virus has also occurred independently on the Pacific Coast from the East Asia-Australasia/Pacific flyways (8).

Canada experienced a wave of HPAI H5N1 outbreaks in the spring of 2022 with millions of wild and farmed birds being infected (9–11). Seabird mortalities in Canada have been particularly severe on the Atlantic Coast over the summer of 2022. With the fall 2022 migration of wild birds from their Arctic breeding grounds to their wintering areas in the south, a new wave of outbreaks spread across Canada and the United States. Wildlife species have been found infected in all provinces and territories, with mass mortality events in wild birds occurring in a broad range of species. The virus has continued to spread within avian populations with reports of HPAI H5N1 appearing from Central and South America by October 2022 (12). This unprecedented global outbreak is causing major pressures on food production, cost, and availability. Over 7 million birds have been culled in Canada, with depopulation of more than 58 million in the United States (13,14). Outbreaks continue to profoundly affect commercial bird farms across the world, including in here in Canada.

Mammalian Transmission

The massive scope of avian infections internationally creates abundant opportunities for spillover to mammals, particularly wild mammals. Multiple genotypes within the clade 2.3.4.4b have been sequenced and some have been detected in free-ranging mammals across the globe. Those genotypes harbour mutations in the HA, polymerase basic protein 2 (PB2), and neuraminidase (NA) genes that are associated with increased binding to human host cell influenza virus receptors, increased adaptation of avian polymerase activity in mammalian cells, and/or increased virulence (15). Viruses with mammalian adaptations such as the mutations PB2-E627K, E627V, and D701N were found in the brain of various carnivores in Europe and Canada (16,17).

This virus can and has infected multiple species, including skunks, foxes, bears, mink, seals, porpoises, sea lions, and dolphins (18). Most infected mammals presented with severe neurological signs and died from encephalitis or meningoencephalitis; however, it is likely that milder disease was also present (and likely more prevalent) because wildlife testing is biased towards severely infected or dead animals. Given the limited scope of surveillance of sick and dead wildlife, it is also assumed that identified infections represent only a minority of spillovers. Mink farms in Spain have been infected and thousands of animals culled, and there has also been substantial sea lion die offs (19,20). This interspecies spillover is of significant concern and highlights the risk of reassortment with swine or human influenza viruses. In vitro and in vivo analysis must continue on circulating strains to ensure strains with enhanced mammalian fitness and transmission are quickly identified (21).

Human Infection and Importance of Health care Provider Awareness

To date this specific clade of H5N1 virus has been identified in less than 10 humans. In addition to the first mild case in the United Kingdom, a second asymptomatic case was reported in April 2022 in the United States and additional cases have occurred in China, Vietnam, Ecuador, and Chile (22). Most cases to date have been mild or asymptomatic; however, in recent months, severe cases have occurred. All severely affected human cases had direct exposure to poultry. Clinicians must be aware of the risks this zoonotic outbreak represents and consider HPAI virus infection in any individual with acute febrile respiratory disease or unexplained neurological diseases in the context of exposure to birds or sick wildlife in the previous 10–14 days (so asking about animal exposures is key). Conjunctivitis and gastrointestinal symptoms have also been reported in humans infected with other avian H5 strains. Suspect cases of H5N1 (with epidemiologic risk factors through recent exposure to avian influenza and clinical symptoms) should be reported to local public health and specimens collected for diagnostic testing. Routine testing will probably identify avian influenza strains as an influenza A, so it is important to notify the laboratory in order that subtyping of positive influenza A virus samples can be performed for confirmation. The best specimens for diagnostic testing for H5N1 are nasopharyngeal or oropharyngeal swabs, bronchioalveolar washes, conjunctival swabs, or tracheal aspirates (23). In patients with severe disease, lower respiratory tract specimens (eg, bronchioalveolar washes) should be obtained as a negative upper respiratory tract specimen does not preclude lower respiratory tract disease.

A One Health Approach

Wild birds will continue to be a source for novel influenza viruses with potential to infect and adapt to human and other mammalian hosts. The emergence of other zoonotic pathogens over the last decade causing widespread epidemics, including Ebola virus, Zika virus, SARS-CoV-2, and Mpox further highlights the intersection between humans, other animals, and their environment. Furthermore, there are major gaps in our understanding of the impact of climate disruption on the ecology and population dynamics of HPAI relative to other infectious diseases, such as vector borne illness (24). HPAI has already had a substantial impact on Canadian wildlife and the poultry industry, and consequently the animal health sector is heavily engaged in prevention, surveillance, and outbreak management. The Canadian Food Inspection Agency (CFIA), Public Health Agency of Canada (PHAC), and provincial authorities have put in place recommendations to prevent transmission between wildlife and domestic poultry, and to monitor the disease in Canada (25,26). Nonetheless, there has been limited preparedness and knowledge dissemination within the human health care sector. At the ground level, awareness should be raised among frontline practitioners most likely to encounter patients with severe febrile respiratory or neurological syndromes of unknown etiology and epidemiological risk factors for infection with HPAI. In addition, now is the time to implement enhanced surveillance among humans by strengthening public health and laboratory capacity to detect, report, and investigate cases of HPAI before the virus becomes established in human populations and to enhance coordination of surveillance and reporting among the human and animal health sectors. Strategic surveillance with counterparts in the animal health sector can facilitate a focus on regions and populations at highest risk based on the epidemiology of HPAI among animals. Additionally, now is also the time to fortify clinical trials, laboratory biocontainment, and other research capacity in collaboration with researchers in agricultural and wildlife animal health to identify and develop non-pharmaceutical and pharmaceutical countermeasures. Collaborative efforts on HPAI between human and veterinary health practitioners also stand to benefit other inter-species concerns, including antimicrobial resistance and vector-borne diseases. There is a clear window of opportunity to mitigate further impact of HPAI, and this may also represent a turning point in how we approach zoonotic diseases in Canada and mitigate the effects of some of these pathogens.

Contributors:

Methodology, C Renaud, A Osborn, S Mubareka; Investigation, C Renaud, A Osborn, S Mubareka; Writing – Original Draft: C Renaud, A Osborn; Writing – Review & Editing: EJ Parmley, T Hatchette, J Leblanc, JS Weese, V Misra, D Yamamura, S Forgie, S Renwick, D Webster; Visualization, C Renaud, A Osborn, S Mubareka; Supervision, C Renaud, A Osborn, S Mubareka; Project Administration, C Renaud.

Ethics Approval:

N/A

Informed Consent:

N/A

Registry and the Registration No. of the Study/Trial:

N/A

Data Accessibility:

All data will not be made publicly available. Researchers who require access to the study data can contact the corresponding author for further information.

Funding:

No funding was received for this work.

Disclosures:

S Forgie reports support from AMMI Canada to attend their board meeting in Toronto, Canada, April 2023, and a previous leadership role at AMMI Canada. TF Hatchette reports grants from GSK/Pfizer, Dalhousie Pharmacy Fund, Drug Evaluation Alliance of NS, CIHR/CIRN, NSERC, COVID-19 Immunity Task Force, NIH, Genome Atlantic, Nova Scotia COVID-19 Health Research Coalition Funding Competition, NSHA Research Fund, and an IWK Project Grant; consulting fees from RockDoc; speaker fees from Sanofi; and past leadership roles at AMMI Canada and Canadian Public Health Laboratory Network. D Yamamura reports a previous leadership role at AMMI Canada.

Peer Review:

This manuscript has been peer reviewed.

Animal Studies:

N/A

Funding Statement

Funding: No funding was received for this work.