ArticlePDF AvailableLiterature Review

Recent Changes in Patterns of Mammal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus Worldwide

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  • CONICET National Scientific and Technical Research Council

Abstract and Figures

We reviewed information about mammals naturally infected by highly pathogenic avian influenza A virus subtype H5N1 during 2 periods: the current panzootic (2020-2023) and previous waves of infection (2003-2019). In the current panzootic, 26 countries have reported >48 mammal species infected by H5N1 virus; in some cases, the virus has affected thousands of individual animals. The geographic area and the number of species affected by the current event are considerably larger than in previous waves of infection. The most plausible source of mammal infection in both periods appears to be close contact with infected birds, including their ingestion. Some studies, especially in the current panzootic, suggest that mammal-to-mammal transmission might be responsible for some infections; some mutations found could help this avian pathogen replicate in mammals. H5N1 virus may be changing and adapting to infect mammals. Continuous surveillance is essential to mitigate the risk for a global pandemic.
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Since last century, highly pathogenic avian inuenza
(HPAI) viruses have caused diverse waves of infec-
tion (1). However, the ongoing panzootic event (2020–
2023) caused by HPAI A(H5N1) virus could become
one of the most important in terms of economic losses,
geographic areas affected, and numbers of species and
individual animals infected (14). This pathogen ap-
pears to be emerging in several regions of the world
(e.g., South America); it has caused death in domestic
and wild birds but also in mammals (2,5,6). This trend
is of great concern because it may indicate a change in
the dynamics of this pathogen (i.e., an increase in their
range of hosts and the severity of the disease) (3).
H5N1 has affected several mammal species since
2003 (6,7), thus raising concern because H5N1 mam-
malian adaptation could represent a risk not only for
diverse wild mammals but also for human health (8
10). Unfortunately, information about this topic, es-
pecially related to the current panzootic (2020–2023),
is disperse and available often only in gray literature
(e.g., databases and ofcial government websites).
This fact complicates access and evaluation for many
stakeholders working on the front lines (e.g., wildlife
managers, conservationists, and public health author-
ities at regional and local levels).
For this article, we compiled and analyzed in-
formation from scientic literature about mammal
species, including humans, naturally affected by the
current panzootic event and compared those ndings
with the outcomes of previous waves of H5N1 infec-
tion. We focus particularly on the species infected,
their habitat, phylogeny, and trophic level, and the
sources of infection, virus mutations, clinical signs,
and necropsy ndings associated with this virus.
We also address potential risks for biodiversity and
human health.
Methods
We compiled scientic information on mammals in-
fected by H5N1 virus through October 2023. We con-
sidered only scientic information on mammal spe-
cies infected naturally (i.e., experimental studies were
not included). We performed 2 systematic searches
in Scopus and Google Scholar, rst using the terms
“H5N1 AND mammal”; this search was divided into 2
periods (1996–2019 and 2020–2023) (Appendix Figure
Recent Changes in Patterns of
Mammal Infection with Highly
Pathogenic Avian Inuenza
A(H5N1) Virus Worldwide
Pablo I. Plaza, Víctor Gamarra-Toledo, Juan Rodríguez Euguí, Sergio A. Lambertucci
444 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024
SYNOPSIS
Author a󰀩liations: Conservation Biology Research Group,
Ecotone Laboratory, Institute of Biodiversity and Environmental
Research (INIBIOMA), National University of Comahue–National
Scientic and Technical Research Council, San Carlos de
Bariloche, Argentina (P.I. Plaza, V. Gamarra-Toledo,
S.A. Lambertucci); Natural History Museum, National University
of San Agustín de Arequipa, Arequipa, Peru (V. Gamarra-Toledo);
Ministry of Health of Tierra del Fuego, Ushuaia, Argentina
(J. Rodríguez Euguí)
DOI: https://doi.org/10.3201/eid3003.231098
We reviewed information about mammals naturally in-
fected by highly pathogenic avian inuenza A virus
subtype H5N1 during 2 periods: the current panzootic
(2020–2023) and previous waves of infection (2003–
2019). In the current panzootic, 26 countries have re-
ported >48 mammal species infected by H5N1 virus;
in some cases, the virus has a󰀨ected thousands of in-
dividual animals. The geographic area and the number
of species a󰀨ected by the current event are consider-
ably larger than in previous waves of infection. The most
plausible source of mammal infection in both periods ap-
pears to be close contact with infected birds, including
their ingestion. Some studies, especially in the current
panzootic, suggest that mammal-to-mammal transmis-
sion might be responsible for some infections; some mu-
tations found could help this avian pathogen replicate in
mammals. H5N1 virus may be changing and adapting to
infect mammals. Continuous surveillance is essential to
mitigate the risk for a global pandemic.
Mammal Infection with HPAI H5N1 Worldwide
1, 2, https://wwwnc.cdc.gov/EID/article/30/3/23-
1098-App1.pdf). We then performed an additional
search with no time restriction using the following
key terms: “H5N1 OR HPAI OR Highly Pathogenic
Avian Inuenza AND mammal OR unusual host.”
This additional search contributed no new articles on
the study topic (Appendix Figure 3). We also adopted
a snowball approach, examining all the references in
the articles we found in our searches. We included
review articles only if they contributed new informa-
tion about mammal species infected naturally with
H5N1; we excluded articles based on serologic sur-
veys because of the difculty in determining when
infection occurred, which can introduce uncertainty
into the diagnosis (11).
To obtain additional information on the current
panzootic event, we also searched the following of-
cial databases: World Organisation for Animal Health
(6), the US Department of Agriculture’s Animal and
Plant Health Service (12), and the United Kingdom’s
Animal and Plant Health Agency (13). To obtain in-
formation about humans affected by this pathogen
we used information provided by the World Health
Organization (14). We constructed a map with the
countries with reports of mammal infections (Figure
1) and the phylogeny of mammal species affected by
H5N1 (Figures 2, 3) by using iTOL version 5, follow-
ing Letunic and Bork (15), from DNA sequence data
available in Upham et al. (16). We retrieved the con-
servation statuses of infected mammals from Inter-
national Union for Conservation of Nature Red List
of Threatened Species (17) and information on their
diets from that database and MammalBase (18).
Results and Discussion
Scientic Information Available
We found 59 scientic articles on mammals infected
naturally by H5N1 virus, 23 from previous waves of
infection (up to 2019) and 36 from the current panzo-
otic event (Appendix Figure 1, 2). The articles report-
ing mammals infected naturally in previous waves
were published during 2004–2018, whereas those ad-
dressing the current panzootic were published dur-
ing 2021–2023. The current panzootic has thus gen-
erated more articles in 3 years than all the previous
waves of infection (published over a 15-year period).
This fact suggests increased general interest in emerg-
ing pathogens affecting biodiversity and mammals
(wild and farmed) and also that the current panzootic
event is causing greater concern and having a greater
effect than previous ones (considering the geographic
regions and mammal species affected) (4).
Geographic Localization of Information and
Mammal Species A󰀨ected
During previous waves of infection, 10 countries re-
ported mammals (not including humans) naturally
infected by H5N1 (5 countries in Asia, 3 in Europe,
and 2 in Africa) (Figure 1, panel A; Appendix Table).
In the current event, 26 countries have reported infor-
mation on mammals (not including humans) infected
by this virus; most information is from Europe (17
countries), followed by South America (5 countries),
North America (2 countries), and Asia (2 countries)
(Figure 1, panel B; Appendix Table). To the best of
our knowledge, for the current outbreak, no informa-
tion is available on mammals from other parts of the
world, which can probably be explained by a lack of
testing or reporting of cases. Our review suggests that
H5N1 virus is expanding its geographic range to new
continents such as North and South America (Figure
1). This fact is of concern because when an emerging
pathogen reaches naive populations, the consequenc-
es for biodiversity can be catastrophic, especially for
threatened species (19).
We found that previous waves of infection af-
fected several mammals around the world (7,20); for
example, tigers (Panthera tigris), leopards (Panthera
pardus), domestic cats (Felis catus), domestic dogs
(Canis lupus familiaris), Owston’s palm civet (Chroto-
gale owstoni), stone martens (Martes foina), plateau pi-
kas (Ochotona curzoniae), minks (Neovison vison), and
raccoon dogs (Nyctereutes procyonoides) (Appendix
Table). All the mammal species affected were terres-
trial or semiaquatic species (Figure 2, panel A). Most
mammals infected during previous waves (75%; n =
9) belong to the order Carnivora, whereas the remain-
der correspond to the Lagomorpha, Artiodactyla, and
Perissodactyla orders (Figure 2, panel B). Infected
mammal species included top predators (e.g., tigers
and leopards) and some mesopredators (e.g., minks)
(Appendix Table). Most species infected in previous
waves were carnivores (n = 6) and omnivores (n = 4),
followed by herbivores (n = 2) (Figure 2, panel C; Ap-
pendix Table).
So far, in the current panzootic, >48 mammal
species from disparate regions of the world have
been reported as naturally infected by H5N1 (Ap-
pendix Table). Most of those species (n = 35) are ter-
restrial or semiaquatic mammals (Figure 3, panel A;
Appendix Table), but 13 species of marine mammals
also were affected, resulting in massive deaths (up
to thousands of individual animals) in geographic
regions such as Peru, Chile, and Argentina (Figure
3, panel A; Appendix Table). Of the total number of
mammals infected, 81% (n = 39) belong to the order
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024 445
SYNOPSIS
Carnivora, and the remainder correspond to Didel-
phimorphia, Rodentia, and Cetartiodactyla (Figure
3, panel B). Infected mammal species include top
predators (e.g., mountain lion [Puma concolor]) and
several mesopredators (e.g., red fox [Vulpes vulpes])
(Appendix Table). Most mammal species infected
are carnivores (n = 34), followed by omnivores (n =
13) and herbivores (n = 1); some of those species (n
= 13) also are considered facultative scavengers (i.e.,
they include in their diet a considerable quantity
of carrion; in our case to be a facultative scavenger
carrion should be named in the diet) (Figure 3, panel
C; Appendix Table).
The species infected in the 2 events show simi-
larities. Most species belong to the order Carnivora
and are top or mesopredators with a carnivorous diet;
some species also are facultative scavengers. How-
ever, in the current panzootic event, the diverse ma-
rine mammals affected have suffered massive deaths
(e.g., American sea lion [Otaria avescens]) (Appendix
Table). Marine mammals have been affected by other
inuenza viruses such as H10N7 (21), but the species
446 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024
Figure 1. Geographic location of mammal species a󰀨ected by highly pathogenic inuenza virus A(H5N1) in previous waves of infection,
2003–2019 (A), and in the current panzootic, 2020–2023 (B).
Mammal Infection with HPAI H5N1 Worldwide
affected and the number of dead individual animals
attributable to the current event is of great concern
(22,23); for example, the proportion of American sea
lions that died in Peru represents 5% of their popula-
tion there (22).
The current panzootic is ongoing, and the num-
ber of species being infected naturally is increasing
(40 new mammal species have been reported as in-
fected by this pathogen during the current panzo-
otic), so the effect on mammal species may continue
to worsen with time. This effect could just be at-
tributable to the current high H5N1 infection rates
throughout the world, which means the virus is
reaching more areas and mammal species living in
these places (i.e., high environmental circulation of
this pathogen) (8). However, the dynamics of the vi-
rus may also be changing (3), in which case its infec-
tivity in unusual species such as mammals is prob-
ably increasing (8). During the nal review process
of this article, 2 additional species were reported to
be infected by this virus in the United States: the Ab-
ert’s squirrel (Sciurus aberti) and the polar bear (Ur-
sus maritimus) (newly infected species are not shown
in gures or the Appendix Table) (6).
Source of Infection
Although the source of infection in mammals is
often unknown, most scientic information avail-
able during previous and the current H5N1 event
suggests that the most plausible source of infection
is close contact with infected birds, including their
ingestion, which may occur through predation of
sick individual animals or scavenging on carcasses.
For instance, in the year 2004, a total of 147 tigers
and 2 leopards housed in zoos in Thailand became
infected and died after consuming infected chicken
carcasses (24,25). In China, this infection source
was also associated with the death of a tiger in 2013
(26) and a lion in 2016 (27). In the current panzootic,
the rst case of H5N1 infection in minks in Spain
was probably caused by contact with infected birds
(perhaps gulls) (9). Ingestion of infected bird car-
casses was probably the route of infection of red
foxes in the Netherlands, Finland, and Japan dur-
ing 2020–2022 (2831), American sea lions in Peru
in 2023 (22), diverse mesocarnivores in Canada
during 2021–2022 (32) and otters (Lutra lutra) and
a lynx (Lynx lynx) in Finland in 2021–2022 (31). Of
concern, studies in infected tigers, farmed minks,
and social species such as American sea lions, raise
an alarm that mammal-to-mammal transmission
may have occurred (9,22,24,33), but further re-
search is needed to conrm this possibility.
If mammal-to-mammal transmission occurs dur-
ing the current H5N1 panzootic, such transmission
could imply that the virus mutated to enable virus
replication in mammal tissues (9). Some researchers
have reported mutations compatible with adapta-
tion to mammal replication (9,25,33,34), which is con-
cerning and requires attention. However, evaluating
whether those mutations happen in wild birds before
mammal infections or arise de novo in mammals after
infection is important.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024 447
Figure 2. Characteristics of mammal species a󰀨ected worldwide
by highly pathogenic inuenza virus A (H5N1) in previous waves
of infection (2003–2019). A) Habitat of mammal species a󰀨ected
by H5N1. B) Phylogeny of mammal species a󰀨ected (tree
constructed using iTOL version 5 following Letunic and Bork
[15], from DNA sequence data available in Upham et al. [16]).
C) Trophic level (facultative scavenger, carnivore, omnivore, or
herbivore) of mammalian species a󰀨ected worldwide by H5N1.
SYNOPSIS
Mutations Found
Through sequencing of the H5N1 viruses infecting
mammals, some relevant mutations such as E627K
in polymerase basic protein 2 (PB2) (PB2-E627K) and
D701N in polymerase basic protein 2 (PB2) (PB2-
D701N) have been found in previous waves and
in the current panzootic (Appendix Table). Those
mutations are commonly associated with virulence
and efciency in the replication of this pathogen in
mammals (31,33,35). For instance, during 2004–2005,
in Thailand, the isolated H5N1 viruses that infected
tigers, a domestic cat, a domestic dog, and a leop-
ard contained the PB2-E627K mutation (25,35,36).
In the current panzootic, red foxes from the Neth-
erlands also showed the mammalian adaptation of
PB2-E627K (28). In viruses collected from red foxes,
an otter, and a lynx in Finland in 2021–2022, the PB2-
E627K and PB2-D701N mutations were identied
(the latter mutation was reported in 1 red fox and 1
lynx in Finland) (31). Similarly, in the current pan-
zootic, red foxes, otters, and polecats (Mustela puto-
rius) in the Netherlands, and red foxes in Canada,
and the United States had the PB2-E627K mutation
(8,32,37). The PB2-E627K and PB2-D701N mutations
were also detected in harbor seals (Phoca vitulina) in
the United States (34), and the latter mutation was
found in South American sea lions in Peru (33), and
in a red fox in Canada (32). In both previous and
current events, other mutations meriting further re-
search were also found in diverse mammal species,
including terrestrial, semiaquatic, and marine mam-
mals (Appendix Table).
Mutations that facilitate replication of the virus in
mammal hosts (e.g., enhancing polymerase activity in
mammal cells), such as PB2-E627K and PB2-D701N,
could be of concern (8,31,33). Potential mutations
must be continuously scrutinized to detect whether
the H5N1 virus is adapting to mammal-to-mammal
transmission. This approach is important for wildlife
conservation because if such transmission occurs, the
consequences for threatened mammal species could
be severe (e.g., threatened South American sea lion
deaths in Peru [22]). In addition, mutations must be
monitored for changes that may favor transmission to
and between humans, which would increase the risk
for a pandemic.
Clinical Signs of H5N1 in Mammals
The most common clinical signs reported in infected
mammals, both in previous waves and the current
H5N1 panzootic, are neurologic and respiratory. For
instance, in 2005, an infected Owston’s civet in Viet-
nam showed loss of appetite and neurologic signs
such as convulsions and paralysis; the same clinical
signs were reported in a stone marten in Germany in
2006 (38,39). Similarly, hundreds of infected tigers in
a zoo in Thailand showed respiratory and neurologic
signs before they died (24). In the current panzootic
event, infected minks from Spain manifested loss of
appetite, hyper salivation, depression, bloody snout,
and neurologic signs such as ataxia and tremors (9).
American sea lions in Peru and harbor seals in the
448 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024
Figure 3. Characteristics of mammal species a󰀨ected worldwide
by highly pathogenic inuenza virus A (H5N1) the current
panzootic (2020–2023). A) Habitat of mammal species a󰀨ected
by H5N1. B) Phylogeny of mammal species a󰀨ected (tree
constructed using iTOL version 5 following Letunic and Bork
[15], from DNA sequence data available in Upham et al. [16]).
C) Trophic level (facultative scavenger, carnivore, omnivore,
or herbivore) of mammal species a󰀨ected worldwide by H5N1.
Some of the omnivorous and carnivorous mammals included in
the pyramid (n = 13) also consume carrion; thus, they are also
considered to be facultative scavengers and are incorporated in
the upper part of the pyramid.
Mammal Infection with HPAI H5N1 Worldwide
United States showed respiratory signs (dyspnea
and whitish secretions in nares) and neurologic signs
(tremors and convulsions) (22,34). Red foxes, an ot-
ter, a polecat, and a badger (Meles meles) in the Neth-
erlands had neurologic signs such as convulsions
and head shaking (8,30). In Finland, an infected otter
was also reported to have a set of neurologic signs
(31). Finally, in the United States and Canada, sev-
eral mammals manifested neurologic and respiratory
signs (32,37). Those ndings suggest that H5N1 virus
has neurotropism in mammals, as reported in birds
(6,28), causing severe disease and pathologic lesions
(e.g., encephalitis); brain samples should be included
in wildlife surveillance programs for reliable detec-
tion of the H5N1 virus in mammals (8).
Although neurologic and respiratory signs are
commonly reported in mammals infected with H5N1,
some species and individual animals show subclinical
disease. For instance, infected pigs (Sus scrofa domesti-
cus) from Indonesia, Nigeria, and China had no signs
of inuenza but tested positive for H5N1 (4042).
Similarly, in Austria, infected domestic cats display
asymptomatic infections (43). Subclinical infections
are concerning because they are not easily detected;
infected individual animals may be transmitting the
virus to other species and even humans, representing
a risk to the ecosystem and human health (40,41).
Necropsy Findings
In previous waves of infection and the current H5N1
panzootic, the most frequently reported anatomo-
pathologic lesions in infected mammals were pneu-
monia and encephalitis. Those kinds of lesions (e.g.,
congestion of brain, meningoencephalitis, hemor-
rhagic lungs, and pleural effusion) were reported in
dead tigers in Thailand and China during 2004–2014
(24,26,44), in a lion in China in 2016 (27), and in cats
and dogs infected naturally in Thailand in 2004
(45,46). In the current panzootic, for instance, red fox-
es from the Netherlands had collapsed lungs with a
marbled red aspect; histopathologic analyses showed
a subacute to chronic purulent granulomatous bron-
cho-interstitial pneumonia and nonsuppurative en-
cephalitis with perivascular cufng (28). Red foxes,
polecats, otters, and a badger in the Netherlands also
showed nonsuppurative meningitis, encephalitis, or
meningoencephalitis, all with differences in severity
(8). American sea lions in Peru had congestive brains
compatible with encephalitis (22). A porpoise (Phocoe-
na phocoena) in Sweden manifested meningoencepha-
litis (47). Similar ndings, meningoencephalitis and
pneumonia, were also found in mammals in Finland,
the United States, and Canada (31,32,37).
Those ndings suggest that respiratory and neu-
rologic lesions are the most common pathologies of
necropsied mammals infected with H5N1 in both
previous waves of infection and the current panzo-
otic. The lesions largely explain the neurologic and re-
spiratory signs observed in mammals affected by this
virus. Complete necropsies of infected mammals may
help determine whether those anatomopathologic
ndings are frequent and pathognomonic for this dis-
ease in every species and most individual animals, as
preliminary results suggest.
Risks for Biodiversity
The current panzootic is affecting a larger number
of species around the world than previous waves of
H5N1 infection, and some are of conservation con-
cern. Previous waves affected 2 endangered and 2
vulnerable species (Appendix Table). The current
panzootic has so far affected 4 near threatened, 4 en-
dangered, 3 vulnerable, and 1 critically endangered
species (Appendix Table); this emerging pathogen
may affect species of conservation concern, exacerbat-
ing their situation.
In general, most mortality events associated with
the current panzootic appear to affect few individual
animals and in only certain areas; thus far, large pop-
ulations have not been affected in the way wild birds
have been affected (4,6). However, this virus is sus-
pected of producing massive deaths in some marine
mammals; for example, >20,000 South American sea
lions were reported to have died suddenly, and many
individual animals tested positive for H5N1 (6,22,23).
This fact raises concern as to the potential effect of this
virus on the demography of some threatened mam-
mal populations. This emerging pathogen represents
a new species invading and impacting new environ-
ments and species and could therefore constitute a
new threat for diverse species currently threatened by
human action (e.g., land use change, contamination,
and habitat loss) (19,48).
Potential Risks for Human Health
During 2003–2023, a total of 878 humans tested posi-
tive for the H5N1 virus, and 458 deaths were report-
ed, indicating a lethality of 52% (14). During 2003–
2019, most human cases came from Asia and Africa,
particularly from China (n = 53), Egypt (n = 359), and
Indonesia (n = 200). From 2020 through July 2023,
human cases of H5N1 infection occurred in diverse
countries, such as Laos (1 case), India (1 case), United
Kingdom (4 cases), China (2 cases), the United States
(1 case), Vietnam (1 case), Spain (2 cases), Ecuador
(1 case), Chile (1 case), and Cambodia (2 cases) (14).
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024 449
SYNOPSIS
Those recent cases resulted in >3 deaths (14). Of note,
this zoonotic virus has produced human cases in new
geographic areas, such as South America.
The spillover to humans has been associated with
close contact between humans and infected animals,
particularly poultry; this kind of contact is relatively
common in some geographic regions (even close con-
tact between dead mammals and humans, as in Peru
[22]). So far, no evidence indicates human-to-human
transmission, and the risk for a pandemic event still
seems low (8). However, one of the most severe inu-
enza viruses to have affected humans (i.e., Spanish in-
uenza [1918–1919]) developed from an avian inuen-
za virus that adapted to humans (49), a fact that should
be considered when assessing the spillover risk.
Mutations in the virus found in diverse mammal
species, especially in the current panzootic, are of
great concern. For instance, the T271A mutation re-
ported in minks in Spain is also present in the H1N1
that produced a pandemic in 2009 (9). Similarly, the
PB2-E627K mutation found in this virus in diverse
geographic areas could indicate an adaptation for rep-
lication in mammals (28,31). Moreover, some infected
species, such as minks, may act as a mixing vessel for
interspecies transmission between birds, mammals,
and humans (9). Mutations and infections with H5N1
in potential mixing-vessel species (e.g., minks and
wild and domestic pigs) should be followed closely
because of the potential risk to human health.
Final Considerations
Given the magnitude of the current H5N1 panzootic,
continuous surveillance is necessary to identify any
increase in risk to biodiversity and human health. It
is therefore essential that all affected countries share
all their available information (e.g., genomic data
of the H5N1 virus, species, and number of individ-
ual animals affected). We urge that all ndings be
shared quickly. International collaboration must be
intensied to obtain rapid results; some less-devel-
oped regions have technologic and logistic barriers
that hinder the production and analysis of informa-
tion on the impact of this virus, and they may need
help. There is a need for strong collaborative work
between countries and institutions in preparation
for any spillover that may lead to a mammalian pan-
zootic or human pandemic.
It is fundamental that we rethink the interface be-
tween humans, domestic animals, and wild animals
to prevent the emergence of dangerous pathogens
that affect biodiversity and human health (48). Gov-
ernments must assume responsibility for protecting
biodiversity and human health from diseases caused
by human activities, particularly diseases originating
from intensive production (50), such as this H5N1 avi-
an inuenza virus. If we hope to conserve biodiversity
and protect human health, we must change the way
we produce our food (poultry farming, in this specic
case) and how we interact with and affect wildlife.
Financial support was provided by Consejo Nacional de
Investigaciones Cientícas y Técnicas, Agencia Nacional
de Promoción Cientíca y Tecnológica (grant no.
PICT-2021-TI-00039), Universidad Nacional del Comahue
(project 04/B227, grant to S.A.L.), and Aves Argentinas
(grant to P.P.).
About the Author
Dr. Plaza is a veterinarian and research associate at the
Conservation Biology Research Group, Ecotone
Laboratory, Institute of Biodiversity and Environmental
Research (INIBIOMA), National University of
Comahue–National Scientic and Technical Research
Council, San Carlos de Bariloche, Argentina. His primary
research interests include wildlife health and epidemiology,
human–wildlife interactions, and animal conservation.
References
1. Shi J, Zeng X, Cui P, Yan C, Chen H. Alarming situation of
emerging H5 and H7 avian inuenza and effective control
strategies. Emerg Microbes Infect. 2023;12:2155072.
https://doi.org/10.1080/22221751.2022.2155072
2. Wille M, Barr IG. Resurgence of avian inuenza virus.
Science. 2022;376:459–60. https://doi.org/10.1126/
science.abo1232
3. Harvey JA, Mullinax JM, Runge MC, Prosser DJ. The
changing dynamics of highly pathogenic avian inuenza
H5N1: next steps for management and science in North
America. Biol Conserv. 2023;282:110041. https://doi.org/
10.1016/j.biocon.2023.110041
4. Adlhoch C, Fusaro A, Gonzales JL, Kuiken T,
Mirinaviciute G, Niqueux É, et al.; European Food Safety
Authority, European Centre for Disease Prevention and
Control, European Union Reference Laboratory for Avian
Inuenza. Avian inuenza overview March–April 2023.
EFSA J. 2023;21:e08039.
5. Gamarra-Toledo V, Plaza PI, Angulo F, Gutiérrez R,
García-Tello O, Saravia-Guevara P, et al. Highly pathogenic
avian inuenza (HPAI) strongly impacts wild birds in Peru.
Biol Conserv. 2023;286:110272. https://doi.org/10.1016/
j.biocon.2023.110272
6. World Organization for Animal Health. WAHIS: World
Animal Health Information System. 2023 [cited 2023 Oct 30].
https://wahis.woah.org
7. Reperant LA, Rimmelzwaan GF, Kuiken T. Avian inuenza
viruses in mammals. Rev Sci Tech. 2009;28:137–59.
https://doi.org/10.20506/rst.28.1.1876
8. Vreman S, Kik M, Germeraad E, Heutink R, Harders F,
Spierenburg M, et al. Zoonotic mutation of highly pathogenic
avian inuenza H5N1 virus identied in the brain of
multiple wild carnivore species. Pathogens. 2023;12:168.
https://doi.org/10.3390/pathogens12020168
450 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024
Mammal Infection with HPAI H5N1 Worldwide
9. Agüero M, Monne I, Sánchez A, Zecchin B, Fusaro A,
Ruano MJ, et al. Highly pathogenic avian inuenza A(H5N1)
virus infection in farmed minks, Spain, October 2022. Euro
Surveill. 2023;28:2300001. https://doi.org/10.2807/
1560-7917.ES.2023.28.3.2300001
10. Kupferschmidt K. Bird u spread between mink is a
‘warning bell’. Science. 2023;379:316–7. https://doi.org/
10.1126/science.adg8342
11. Horimoto T, Maeda K, Murakami S, Kiso M,
Iwatsuki-Horimoto K, Sashika M, et al. Highly pathogenic
avian inuenza virus infection in feral raccoons, Japan.
Emerg Infect Dis. 2011;17:714–7. https://doi.org/10.3201/
eid1704.101604
12. US Departament of Agriculture. 2022–2023 Detections of
highly pathogenic avian inuenza in mammals [cited 2023
Oct 30]. https://www.aphis.usda.gov/aphis/ourfocus/
animalhealth/animal-disease-information/avian/
avian-inuenza/hpai-2022/2022-hpai-mammals
13. United Kingdom Animal and Plant Health Agency.
Conrmed ndings of inuenza of avian origin in non-avian
wildlife [cited 2023 Oct 30]. https://www.gov.uk/
government/publications/bird-u-avian-inuenza-ndings-
in-non-avian-wildlife/conrmed-ndings-of-i]nuenza-of-
avian-origin-in-non-avian-wildlife
14. World Health Organization. Cumulative number of
conrmed human cases for avian inuenza A(H5N1)
reported to WHO, 2003–2023, 3 October 2023. 2023 [cited
2023 Oct 30]. https://www.who.int/publications/m/item/
cumulative-number-of-conrmed-human-cases-for-avian-
inuenza-a(h5n1)-reported-to-who--2003-2023--3-october-2023
15. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an
online tool for phylogenetic tree display and annotation.
Nucleic Acids Res. 2021;49(W1):W293–6. https://doi.org/
10.1093/nar/gkab301
16. Upham NS, Esselstyn JA, Jetz W. Inferring the mammal tree:
species-level sets of phylogenies for questions in ecology,
evolution, and conservation. PLoS Biol. 2019;17:e3000494.
https://doi.org/10.1371/journal.pbio.3000494
17. IUCN. IUCN red list of threatened species. 2023 [cited 2023
Oct 30]. https://www.iucnredlist.org
18. MammalBase. Database of recent mammals [cited 2023 Oct
30]. https://www.mammalbase.net/mb
19. Dobson A, Foufopoulos J. Emerging infectious pathogens of
wildlife. Philos Trans R Soc Lond B Biol Sci. 2001;356:1001–
12. https://doi.org/10.1098/rstb.2001.0900
20. Root J, Shriner S. Avian inuenza A virus associations in
wild, terrestrial mammals: a review of potential synanthropic
vectors to poultry facilities. Viruses. 2020;12:1352.
https://doi.org/10.3390/v12121352
21. Bodewes R, Bestebroer TM, van der Vries E, Verhagen JH,
Herfst S, Koopmans MP, et al. Avian inuenza A(H10N7)
virus–associated mass deaths among harbor seals.
Emerg Infect Dis. 2015;21:720–2. https://doi.org/10.3201/
eid2104.141675
22. Gamarra-Toledo V, Plaza P, Inga G, Gutiérrez R,
Garcia-Tello O, Valdivia-Ramirez L, et al. Mass mortality
of sea lions caused by highly pathogenic inuenza virus
(H5N1) in South America. Emerg Infect Dis. 2023;29:2553–6.
https://doi.org/10.3201/eid2912.230192
23. OFFLU Ad-Hoc Group on HPAI H5 in Wildlife of South
America and Antarctica. Southward expansion of high
pathogenicity avian inuenza H5 in wildlife in South
America: estimated impact on wildlife populations, and risk
of incursion into Antarctica. 2023 [cited 2023 Oct 30].
https://www.ofu.org/wp-content/uploads/2023/08/
OFFLU-statement-HPAI-wildlife-South-America-20230823.pdf
24. Thanawongnuwech R, Amonsin A, Tantilertcharoen R,
Damrongwatanapokin S, Theamboonlers A, Payungporn S,
et al. Probable tiger-to-tiger transmission of avian inuenza
H5N1. Emerg Infect Dis. 2005;11:699–701. https://doi.org/
10.3201/eid1105.050007
25. Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier RA,
Amonsin A, Payungporn S, et al. Avian inuenza H5N1
in tigers and leopards. Emerg Infect Dis. 2004;10:2189–91.
https://doi.org/10.3201/eid1012.040759
26. He S, Shi J, Qi X, Huang G, Chen H, Lu C. Lethal infection
by a novel reassortant H5N1 avian inuenza A virus in a
zoo-housed tiger. Microbes Infect. 2015;17:54–61.
https://doi.org/10.1016/j.micinf.2014.10.004
27. Chen Q, Wang H, Zhao L, Ma L, Wang R, Lei Y, et al.
First documented case of avian inuenza (H5N1) virus
infection in a lion. Emerg Microbes Infect. 2016;5:e125.
https://doi.org/10.1038/emi.2016.127
28. Bordes L, Vreman S, Heutink R, Roose M, Venema S,
Pritz-Verschuren SBE, et al. Highly pathogenic avian
inuenza H5N1 virus infections in wild red foxes (Vulpes
vulpes) show neurotropism and adaptive virus mutations.
Microbiol Spectr. 2023;11:e0286722. https://doi.org/10.1128/
spectrum.02867-22
29. Hiono T, Kobayashi D, Kobayashi A, Suzuki T, Satake Y,
Harada R, et al. Virological, pathological, and glycovirological
investigations of an Ezo red fox and a tanuki naturally
infected with H5N1 high pathogenicity avian inuenza
viruses in Hokkaido, Japan. Virology. 2023;578:35–44.
https://doi.org/10.1016/j.virol.2022.11.008
30. Rijks JM, Hesselink H, Lollinga P, Wesselman R, Prins P,
Weesendorp E, et al. Highly pathogenic avian inuenza
A (H5N1) virus in wild red foxes, the Netherlands, 2021.
Emerg Infect Dis. 2021;27:2960–2. https://doi.org/10.3201/
eid2711.211281
31. Tammiranta N, Isomursu M, Fusaro A, Nylund M,
Nokireki T, Giussani E, et al. Highly pathogenic avian
inuenza A (H5N1) virus infections in wild carnivores
connected to mass mortalities of pheasants in Finland [cited
2023 Oct 30]. Infect Genet Evol. 2023;111:105423.
32. Alkie TN, Cox S, Embury-Hyatt C, Stevens B, Pople N,
Pybus MJ, et al. Characterization of neurotropic HPAI H5N1
viruses with novel genome constellations and mammalian
adaptive mutations in free-living mesocarnivores in Canada.
Emerg Microbes Infect. 2023;12:2186608. https://doi.org/
10.1080/22221751.2023.2186608
33. Leguia M, Garcia-Glaessner A, Muñoz-Saavedra B, Juarez D,
Barrera P, Calvo-Mac C, et al. Highly pathogenic avian
inuenza A (H5N1) in marine mammals and seabirds in
Peru. Nat Commun. 2023;14:5489. https://doi.org/10.1038/
s41467-023-41182-0
34. Puryear W, Sawatzki K, Hill N, Foss A, Stone JJ, Doughty L,
et al. Highly pathogenic avian inuenza A(H5N1) virus
outbreak in New England seals, United States. Emerg Infect
Dis. 2023;29:786–91. https://doi.org/10.3201/eid2904.221538
35. Amonsin A, Payungporn S, Theamboonlers A,
Thanawongnuwech R, Suradhat S, Pariyothorn N, et al.
Genetic characterization of H5N1 inuenza A viruses
isolated from zoo tigers in Thailand. Virology. 2006;344:480–91.
https://doi.org/10.1016/j.virol.2005.08.032
36. Amonsin A, Songserm T, Chutinimitkul S, Jam-On R,
Sae-Heng N, Pariyothorn N, et al. Genetic analysis of
inuenza A virus (H5N1) derived from domestic cat
and dog in Thailand. Arch Virol. 2007;152:1925–33.
https://doi.org/10.1007/s00705-007-1010-5
37. Elsmo EJ, Wunschmann A, Beckmen KB,
Broughton-Neiswanger LB, Buckles EL, Ellis J, et al.
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024 451
SYNOPSIS
Pathology of natural infection with highly pathogenic avian
inuenza virus (H5N1) clade 2.3.4.4b in wild terrestrial
mammals in the United States in 2022. Emerg Infect Dis.
2023;29:2451–60. https://doi.org/10.3201/eid2912.230464
38. Roberton SI, Bell DJ, Smith GJD, Nicholls JM, Chan KH,
Nguyen DT, et al. Avian inuenza H5N1 in viverrids:
implications for wildlife health and conservation. Proc
Biol Sci. 2006;273:1729–32. https://doi.org/10.1098/
rspb.2006.3549
39. Klopeisch R, Wolf PU, Wolf C, Harder T, Starick E,
Niebuhr M, et al. Encephalitis in a stone marten (Martes foina)
after natural infection with highly pathogenic avian
inuenza virus subtype H5N1. J Comp Pathol. 2007;
137:155–9. https://doi.org/10.1016/j.jcpa.2007.06.001
40. Nidom CA, Takano R, Yamada S, Sakai-Tagawa Y, Daulay S,
Aswadi D, et al. Inuenza A (H5N1) viruses from pigs,
Indonesia. Emerg Infect Dis. 2010;16:1515–23. https://doi.org/
10.3201/eid1610.100508
41. Meseko C, Globig A, Ijomanta J, Joannis T, Nwosuh C,
Shamaki D, et al. Evidence of exposure of domestic
pigs to highly pathogenic avian inuenza H5N1 in Nigeria.
Sci Rep. 2018;8:5900. https://doi.org/10.1038/
s41598-018-24371-6
42. He L, Zhao G, Zhong L, Liu Q, Duan Z, Gu M, et al.
Isolation and characterization of two H5N1 inuenza
viruses from swine in Jiangsu Province of China. Arch
Virol. 2013;158:2531–41. https://doi.org/10.1007/
s00705-013-1771-y
43. Leschnik M, Weikel J, Möstl K, Revilla-Fernández S,
Wodak E, Bagó Z, et al. Subclinical infection with avian
inuenza A (H5N1) virus in cats. Emerg Infect Dis.
2007;13:243–7. https://doi.org/10.3201/eid1302.060608
44. Hu T, Zhao H, Zhang Y, Zhang W, Kong Q, Zhang Z, et al.
Fatal inuenza A (H5N1) virus Infection in zoo-housed
tigers in Yunnan Province, China. Sci Rep. 2016;6:25845.
https://doi.org/10.1038/srep25845
45. Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Meemak N,
Pariyothorn N, et al. Avian inuenza H5N1 in naturally
infected domestic cat. Emerg Infect Dis. 2006;12:681–3.
https://doi.org/10.3201/eid1204.051396
46. Songserm T, Amonsin A, Jam-on R, Sae-Heng N,
Pariyothorn N, Payungporn S, et al. Fatal avian inuenza A
H5N1 in a dog. Emerg Infect Dis. 2006;12:1744–7.
https://doi.org/10.3201/eid1211.060542
47. Thorsson E, Zohari S, Roos A, Banihashem F, Bröjer C,
Neimanis A. Highly pathogenic avian inuenza A(H5N1)
virus in a harbor porpoise, Sweden. Emerg Infect Dis.
2023;29:852–5. https://doi.org/10.3201/eid2904.221426
48. Daszak P, Cunningham AA, Hyatt AD. Emerging infectious
diseases of wildlife—threats to biodiversity and human
health. Science. 2000;287:443–9. https://doi.org/10.1126/
science.287.5452.443
49. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G,
Fanning TG. Characterization of the 1918 inuenza virus
polymerase genes. Nature. 2005;437:889–93. https://doi.org/
10.1038/nature04230
50. Kuiken T, Cromie R. Protect wildlife from livestock diseases.
Science. 2022;378:5.
Address for corresponding author: Pablo I. Plaza, Conservation
Biology Research Group, Ecotone Laboratory, Institute of
Biodiversity and Environmental Research (INIBIOMA), National
University of Comahue–National Scientic and Technical Research
Council, Quintral 1250 (R8400FRF), San Carlos de Bariloche,
Argentina; email: plazapablo@comahue-conicet.gob.ar
452 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 30, No. 3, March 2024
RESEARCH
EID Podcast
Rat Hepatitis E Virus
in Norway Rats,
Ontario, Canada,
2018-2021
Visit our website to listen:
https://bit.ly/3PX20s1
®
Reports of acute hepas caused by rat hep-
as E virus (HEV) raise concerns regarding
the potenal risk for rat HEV transmission to
people and hepas E as an emerging infec-
ous disease worldwide. During 2018–2021,
researchers tested liver samples from 372
Norway rats from southern Ontario, Canada
to invesgate presence of hepas E virus in-
fecon. Overall, 21 (5.6%) rats tested posive
for the virus.
In this EID podcast, Dr. Sarah Robinson, a
postdoctoral researcher at the University of
Guelph, discusses hepas E virus in Norway
rats in Ontario, Canada.
... These IAVs have the potential to cause human-to-human transmission with the acquisition of adaptive mutations (5,6). The H5N1 subtype of the highly pathogenic avian influenza virus (HPAIV) has recently been reported to infect domestic and wild birds, as well as mammals, including humans, worldwide (7)(8)(9). H5N1 virus infection in dairy cattle and transmission to humans through direct and close exposure to infected dairy cattle were reported in the United States in 2024 (10). In addition to H5N1 HPAIVs, various subtypes of avian IAVs, such as H5N6, H7N9, H9N2, and H10N3, and swine IAVs have been reported to be transmitted to humans, causing mild to severe illness (8,11). ...
... The polymerase genes (PB2, PB1, and PA) were not distinguishable on the gel owing to their similar molecular weights. The remaining nine samples (sample no.[3][4][5][6][7][8][9][10][11] showed band patterns different from the expected band sizes, and none of the samples showed clear RT-PCR amplification of all eight IAV segments(Fig. 1). ...
Article
MinION sequencing is widely used to sequence influenza A virus (IAV) genomes; however, the accuracy and utility of this approach, using the latest chemistry to obtain whole viral genome sequences directly from clinical samples, remain insufficiently investigated. We evaluated the sequencing accuracy of combining simultaneous multisegment one-step RT-PCR and MinION sequencing using various subtypes of 13 IAV isolates. The latest R10.4.1 chemistry significantly improved sequencing accuracy, achieving ≥99.993% identity with Illumina MiSeq results and reducing the single nucleotide deletion in homopolymer regions. Applying this method to 11 clinical samples enabled rapid subtype identification and the acquisition of eight full-length IAV genomes. In four of these samples, subtype identification of HA and NA was achieved within 20 min after the start of sequencing and a full-length IAV genome was obtained within 7 h after RNA extraction. However, there was concern that cross barcode misassignment during demultiplexing affected data interpretation, particularly for samples with low viral genome copy numbers. This approach can be used for the rapid identification of IAV subtypes and accurate acquisition of full IAV genome sequences from clinical samples, although careful data analysis is required for the multiplex sequencing of clinical samples with low viral genome copy numbers.
... H5Nx viruses can be both HPAI or LPAI, with HPAI H5Nx (x referring to any NA subtype) viruses commonly having a polybasic cleavage site in the hemagglutinin (HA) protein. HPAI H5Nx clades threaten wild and domestic bird populations, as well as mammals and humans as a zoonotic virus [1]. Moreover, nearly 900 HPAI H5Nx infections in humans have been detected, with nearly half of those diagnosed succumbing to infection (approximately 50% case fatality rate) [2]. ...
... Since March 2024, H5N1 viruses within the 2.3.4.4b clade have caused an unprecedented outbreak in dairy cows in the United States of America. The spread and persistence of H5N1 viruses in mammals raises concerns of H5N1 adapting to mammalian hosts, which could lead to a pandemic in humans [1]. [4]. ...
... This was followed in 2020 by the ongoing global wave of H5N1 viruses harbouring clade 2.3.4.4b H5 14,15 and since 2022, more and more avian and mammalian species have been found to be infected by the currently circulating H5N1 viruses 16,17 . ...
... Certain substitutions in the HA protein can allow it to switch its receptor binding specificity, from avian-type SA-α2,3 (preferentially bound by AIVs) to mammalian-type SA-α2,6 (preferentially bound by human/mammalian IAVs) 28,29 . Beside several substitutions in HA that are required to allow airborne person-to-person transmission, human adaptation also involves substitution E627K in the PB2 subunit of the viral polymerase to enhance viral replication in mammalian cells 16,29 . While most H5 AIVs that have been isolated so far from milk or cattle have not acquired these well-known adaptation markers, they carry several other substitutions that may increase their transmissibility and virulence in mammals 30 . ...
Article
Full-text available
Influenza, a major “One Health” threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission in the USA. This review explores general aspects of influenza A virus (IAV) biology, its interactions with mammalian hosts, and discusses the key considerations for developing vaccines to prevent or curtail IAV infection in the bovine mammary gland and its spread through milk
... Local part of the investigation lasted until the last days of June when cooperative work of regional inspections excluded mammal to mammal transmission (including to humans) as the main route. Most literature on preparedness focuses on national and international collaboration, while regional efforts are overlooked, and we have seen consequences of that in 2023 [87]. Thus, the socalled Situation Definition Phase (assessing, specifying and interpreting the current situation) requires regional expertise and capacities [88]. ...
... The virus is spread through bird faeces, saliva or contaminated food and water but also through ingestion of an infected animal [7]. People in close contact with birds, such as workers on poultry farms and veterinarians, are most at risk of infection. ...
Article
Full-text available
Introduction Global shift in the ecology of highly pathogenic avian influenza strains like H5N1 and the spread of avian influenza to mammals are raising concerns and prompting action in the event of a pandemic. Due to the nature of viruses, a future influenza pandemic is inevitable and preparedness for it vital. The aim of this article is to present the developed strategies for preventing pandemic influenza as a measure of preparedness for the upcoming threat. State of knowledge For public health purposes, influenza is divided into: seasonal, zoonotic and pandemic [1]. Although pandemic influenza spread very rare, it is of great concern due to its global reach and high mortality rate [2]. Health experts are concerned that a future pandemic could be caused by the H5N1 strain of the virus, an infection that can spread from birds to humans [3]. WHO, in collaboration with other institutions, continuously monitors influenza viruses. Based on risk assessment, it issues guidelines, develops surveillance strategies, and establishes a pandemic response plan. As part of preparedness for the next pandemic, specific influenza vaccines are developed and available antiviral drugs are being tested for their effectiveness against strains with pandemic potential. Summary Having appropriate policy and planning in place facilitates early response in order to suppress an influenza outbreak quickly, thus reducing the potentially catastrophic future impacts of a pandemic. Currently available antiviral medicines are mostly effective against the highly pathogenic strains of influenza A virus of concern. The Zoonotic influenza vaccines contains a strain matching the currently circulating clade to ensure protection. Effective plans will not succeed without the will to implement and execute them.
... Habitat loss from extensive bushfires could lead to similar risks 152 Influenza. Influenza A virus is the archetypal pathogen with pandemic potential and, increasingly, a global threat to biodiversity 91,154 . Viral strains undergo genetic drift and reassortment in poultry and other livestock, which also transmit the virus back to wild birds and humans. ...
Article
Avian influenza (AI) virus, and the (HPAI)H5N1 subtype in particular, is a serious problem for many wild bird populations, where devastating losses have been reported. However, AI is not restricted to bird species. Here, a literature search was used to assess the range of animals infected by AI. This included reports in the scientific journals as well as news outlets. As can be seen, infection has been reported in commercial mammals such as cattle and mink where there is close animal-to-animal contact, as well as close contact with humans. Some domestic animals, such as cats, have been reported to be AI virus positive too, again where there is a possibility that conditions will be conducive to animal-to-human transmission. Many animals in the wild have been found to be infected with AI virus, and many of these, perhaps not surprisingly, are marine mammals. Mink-to-mink viral transmission has been suggested to have taken place, but most animals which have been infected have had close contact with birds, often handling or eating carcasses. There are also reports of humans becoming infected, for example, from cattle. Although this overview is intended to be neither comprehensive nor quantitative it is hoped that such information will aid in the management of AI, especially (HPAI)H5N1, in the future.
Preprint
Full-text available
Following reports of HPAI H5N1 infections of dairy cattle in the United States (US) in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies, as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the US has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.
Article
Full-text available
The highly pathogenic avian influenzaH5N1 is an emerging and unexpected threat to many wild animal species, which has implications for ecological processes, ecosystem services and conservation of threatened species. International collaborationand information-sharing is essential for surveillance, early diagnosis and the provision of financial and technical instruments to enable worldwide actions.
Article
Full-text available
We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals 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 showed primarily neurologic 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.
Article
Full-text available
We report a massive mortality of 5,224 sea lions (Otaria flavescens) in Peru that seemed to be associated with highly pathogenic avian influenza A(H5N1) virus infection. The transmission pathway may have been through the close contact of sea lions with infected wild birds. We recommend evaluating potential virus transmission among sea lions.
Article
Full-text available
Highly pathogenic avian influenza (HPAI) A/H5N1 viruses (lineage 2.3.4.4b) are rapidly invading the Americas, threatening wildlife, poultry, and potentially evolving into the next global pandemic. In November 2022 HPAI arrived in Peru, triggering massive pelican and sea lion die-offs. We report genomic characterization of HPAI/H5N1 in five species of marine mammals and seabirds (dolphins, sea lions, sanderlings, pelicans and cormorants). Peruvian viruses belong to lineage 2.3.4.4b, but they are 4:4 reassortants where 4 genomic segments (PA, HA, NA and MP) position within the Eurasian lineage that initially entered North America from Eurasia, while the other 4 genomic segments (PB2, PB1, NP and NS) position within the American lineage (clade C) that circulated in North America. These viruses are rapidly accruing mutations, including mutations of concern, that warrant further examination and highlight an urgent need for active local surveillance to manage outbreaks and limit spillover into other species, including humans.
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