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Passive and active surveillance and identifying specific hosts of H5 HPAIVs. (A) Space-time distribution of provinces reporting H5 HPAIV outbreaks and active surveillance programs and the number of H5 HPAIV strains publicly registered (GISAID and/or IRD) in given provinces during 2014-2017. Province centroids are used to localize total number of H5 HPAIV strains published in each province. * and † indicate H5 HPAIVs detected from human cases of clade 1.1.2 and 2.3.2.1c viruses, respectively. (B) Summary statistics of domestic poultry species and environmental samples positive for H5 HPAIVs in our surveillance program. Number and size of each circle indicates sum of infected individuals.
Source publication
This study aimed to elucidate virus, host and environmental dynamics of Vietnamese H5 highly pathogenic avian influenza viruses (HPAIVs) during 2014–2017. Epidemiologically, H5 HPAIVs were frequently detected in apparently healthy domestic and Muscovy ducks and therefore these are preferred species for H5 HPAIV detection in active surveillance. Vir...
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... programs and identifying specific hosts of H5 HPAIVs. Profiles gathered from passive and active surveillance programs in poultry in Vietnam were reviewed. The choropleth map in Fig. 1A illustrated space-time distribution of provinces reporting H5 HPAIV outbreaks as denoted via passive notification and provinces conducting active surveillance for the period 2014-2017. Outbreaks of disease associated with H5 HPAIVs were reported in all regions (North, Central and South) in each year, indicating that H5 HPAIVs persisted ...
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... in each province that were available in public influenza virus databases were co-plotted in the choropleth map. Within the 4-year period, a substantial number of Vietnamese H5 HPAIV strains (n = 192) were deposited in the public databases. More viruses were deposited in 2014 compared to 2016 in line with the increase in the number of outbreaks (Fig. 1A). These results demonstrate the importance of surveillance for monitoring H5 HPAIVs in Vietnam and its contribution to global influenza ...
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... these, 77 geographically and temporally representative isolates were selected for sequencing (Supplementary Table S3). The results from virus isolation in our active surveillance of apparently healthy birds showed that domestic ducks (51 isolates) and Muscovy ducks (72 isolates) were the species from which H5 HPAIVs were most frequently isolated (Fig. 1B). Likewise, the number of infected birds with other Vietnamese H5 HPAIV strains deposited in global surveillance databases (unknown whether passive or active sources) showed a similar pattern ( Supplementary Fig. S1). Therefore, domestic and Muscovy ducks are preferred species for detection of H5 HPAIVs in active ...
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... results from virus isolation in our active surveillance of apparently healthy birds showed that domestic ducks (51 isolates) and Muscovy ducks (72 isolates) were the species from which H5 HPAIVs were most frequently isolated (Fig. 1B). Likewise, the number of infected birds with other Vietnamese H5 HPAIV strains deposited in global surveillance databases (unknown whether passive or active sources) showed a similar pattern ( Supplementary Fig. S1). Therefore, domestic and Muscovy ducks are preferred species for detection of H5 HPAIVs in active surveillance. ...
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... illustrated that active and passive surveillance system in Vietnam allowed detection of viruses and disease outbreaks although it also demonstrated that some gaps exist that could result in non-detection of viruses. This work significantly contributed to global influenza surveillance via publishing substantial genetic data of detected viruses (Fig. 1A and www.nature.com/scientificreports www.nature.com/scientificreports/ Supplementary Table S3). However, it is also critical to discuss some constraints in the system. For instance, in the passive surveillance program, genetic information of H5 HPAIVs that caused outbreaks remained limited. The majority of virus sequences available in ...
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... sequences available in public databases were derived from active surveillance programs. A human case infected with a clade 1.1.2 virus was reported in a southern province in 2014, but no outbreak case and genetic information of clade 1.1.2 virus were reported in poultry, posing uncertainty about the actual circulation of viruses in this area (Fig. 1A). These examples emphasize the need to further develop surveillance, particularly virus investigation post surveillance and more focus on high risk areas. In addition, close collaboration between veterinary and human health sectors is needed for effective monitoring and control of ...
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... our surveillance, H5 HPAIVs were largely and frequently detected in apparently healthy domestic and Muscovy ducks (Fig. 1B). Role of domestic ducks for H5 HPAIV persistence has been demonstrated 24,25 , but the role of Muscovy ducks remains uncertain. Previous studies have reported that Muscovy ducks were more susceptible to Gs/GD-lineage H5 HPAIVs and vaccination was less effective in preventing infection compared with domestic ducks 26,27 . This result ...
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... that Muscovy ducks were more susceptible to Gs/GD-lineage H5 HPAIVs and vaccination was less effective in preventing infection compared with domestic ducks 26,27 . This result reinforces the epidemiological importance of domestic ducks and justifies further exploration of the role of Muscovy ducks. They remain good targets for active surveillance (Fig. 1B and Supplementary Fig. S1). Moreover, all H5 HPAIVs in our surveillance were isolated in LBMs and LBM-like locations, indicating that LBMs play important roles for virus persistence and dissemination 18,28 . These findings confirmed relatively constant epidemiology of H5 HPAIVs in regards that abundance of waterfowl species and live poultry trading activities ...
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... to domestic terrestrial birds and this was also the case with recent H5 HPAIVs in Vietnam which did not contain any mutation makers associated with mammalian adaptation and/or virulence (Table 1). Nonetheless, the threats to human health are always present; in fact, H5 HPAIVs possessing typical avian phenotypes triggered human infections in 2014 (Fig. 1A) [30][31][32] . This implies complexity of virological and epidemiological interactions and gaps of our understanding H5 HPAIV human infection in ...
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The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this stud...
Citations
... NS1 is a multifunctional viral protein that counteracts the innate immune response of the host, enabling the virus to replicate effectively during infection [69]. All viruses analyzed here lacked NS1 amino acids [80][81][82][83][84] (Supplemental Tables S2 and S3), a deletion that increases the pathogenicity of H5N1 viruses in mice [70]. The amino acids at positions 103 and 106 (equivalent to positions 98 and 101 in NS1∆80-84) are important for binding to CPSF30 [71,72], which affects the nuclear export of poly(A)-containing mRNA and thus influenza virus-mediated shutdown of host cell protein synthesis. ...
Routine surveillance in live poultry markets in the northern regions of Vietnam from 2016 to 2017 resulted in the isolation of 27 highly pathogenic avian H5N1 and H5N6 viruses of 3 different clades (2.3.2.1c, 2.3.4.4f, and 2.3.4.4g). Sequence and phylogenetic analysis of these viruses revealed reassortment with various subtypes of low pathogenic avian influenza viruses. Deep-sequencing identified minor viral subpopulations encoding variants that may affect pathogenicity and sensitivity to antiviral drugs. Interestingly, mice infected with two different clade 2.3.2.1c viruses lost body weight rapidly and succumbed to virus infection, whereas mice infected with clade 2.3.4.4f or 2.3.4.4g viruses experienced non-lethal infections.
... From 2014 to 2018, 1361 viruses were isolated from 15431 cloacal and oropharyngeal samples of domestic birds and environmental samples (Table S1), indicating an AIV prevalence of 8.8% (95% confidence interval: 8.4-9.3). The virological characterization were conducted for some H6 and H9 viruses isolated in Hue province in 2014, H7 viruses isolated in Vinh Long province in 2018, and H5 HPAIVs isolated from 2014 to 2017 in previous studies [18,29,40]. The other isolates were reported only in an epidemiological aspect [19,41] or newly characterized in the present study. ...
The H9 and H6 subtypes of low pathogenicity avian influenza viruses (LPAIVs) cause substantial economic losses in poultry worldwide, including Vietnam. Herein, we characterized Vietnamese H9 and H6 LPAIVs to facilitate the control of avian influenza. The space–time representative viruses of each subtype were selected based on active surveillance from 2014 to 2018 in Vietnam. Phylogenetic analysis using hemagglutinin genes revealed that 54 H9 and 48 H6 Vietnamese LPAIVs were classified into the sublineages Y280/BJ94 and Group II, respectively. Gene constellation analysis indicated that 6 and 19 genotypes of the H9 and H6 subtypes, respectively, belonged to the representative viruses. The Vietnamese viruses are genetically related to the previous isolates and those in neighboring countries, indicating their circulation in poultry after being introduced into Vietnam. The antigenicity of these subtypes was different from that of viruses isolated from wild birds. Antigenicity was more conserved in the H9 viruses than in the H6 viruses. Furthermore, a representative H9 LPAIV exhibited systemic replication in chickens, which was enhanced by coinfection with avian pathogenic Escherichia coli O2. Although H9 and H6 were classified as LPAIVs, their characterization indicated that their silent spread might significantly affect the poultry industry.
... Từ năm 2005 đến nay, vaccine phòng bệnh cúm gia cầm được sử dụng phổ biến tại các tỉnh thuộc khu vực ĐBSCL bao gồm Navet-Vifluvac, Navet-Fluvac 2 và vaccine tái tổ hợp Re-5 và Re-6 (Nguyen et al., 2019). Mỗi loại vaccine khác nhau cho các tỷ lệ bảo hộ khác nhau đối với các phân nhánh khác nhau của virus cúm gia cầm type A/H5. ...
Nghiên cứu được thực hiện nhằm đánh giá tỷ lệ tiêm phòng và đáp ứng miễn dịch sau tiêm của bệnh cúm gia cầm độc lực cao type A/H5 (H5 highly pathogenic avian influenza, H5 HPAI) trên đàn gia cầm của tỉnh Đồng Tháp giai đoạn 2019–2020. Nghiên cứu được tiến hành thông qua thu thập số liệu hồi cứu tình hình tiêm phòng và đáp ứng miễn dịch sau tiêm từ Chi cục Chăn nuôi, Thú y và Thủy sản tỉnh Đồng Tháp. Kết quả cho thấy tỷ lệ tiêm phòng cúm gia cầm type A/H5 có sự khác nhau giữa các huyện/thành phố giai đoạn 2019–2020. Có 6 trong 12 huyện/thành phố có tỷ lệ đàn gia cầm được tiêm phòng dưới 70%. Tỷ lệ tiêm phòng trên vịt cao hơn gà ở các huyện/thành phố. Tỷ lệ đàn đạt bảo hộ sau tiêm phòng tăng từ 59,46% (năm 2019) lên 84,62% (năm 2020). Tỷ lệ bảo hộ trên vịt tăng từ 77,78% (2019) đến 89,05% (2020), cao hơn gà (50,0% năm 2019 và 60,61%, năm 2020). Kết quả nghiên cứu là cơ sở để đánh giá tình hình tiêm phòng và đáp ứng miễn dịch sau tiêm phòng H5, từ đó giúp triển khai các phương án nâng cao công tác tiêm phòng tại các địa phương nhằm kiểm soát hiệu quả H5 HPAI tại tỉnh Đồng Tháp.
... The introduction of new AIVs in northern Vietnam was supposedly related to cross-border transmission, whereas southern Vietnam maintained predominant AIVs [21]. A cross-sectional study on AI focusing on LPAIV was conducted in Vinh Long Province to identify the characteristics of farmers associated with LPAIV infection in poultry. ...
... This situation promoted the reassortment event that led to the antigenic shift. The report on the reassortment of LPAIV with H5N6 HPAIV was released in Vietnam [19,21]. Furthermore, mixing many species and a free-grazing farming model might enhance the frequency of reassortment events [7]. ...
The impact of low pathogenicity avian influenza (LPAI) has been confirmed mainly in farms. Unlike apparent losses caused by the high pathogenicity avian influenza (HPAI), the LPAI impact has been hardly evaluated due to underestimating its spread and damage. In 2019, a questionnaire study was conducted in southern Vietnam to identify the specific risk factors of LPAI virus (LPAIV) circulation and to find associations between husbandry activities and LPAI prevalence. A multilevel regression analysis indicated that keeping Muscovy ducks during farming contributed to LPAIV positivity [Odds ratio=208.2 (95% confidence interval: 13.4-1.1×104)]. In cluster analysis, farmers willing to report avian influenza (AI) events and who agreed with the local AI control policy had a slightly lower risk for LPAIV infection although there was no significance in the correlation between farmer characteristics and LPAI occurrence. These findings indicated that keeping Muscovy ducks without appropriate countermeasures might increase the risk of LPAIV infection. Furthermore, specific control measures at the local level are effective for LPAIV circulation, and the improvement of knowledge about biosecurity and attitude contributes to reducing LPAI damage.
... The 2.3.4.4 H5N6 HPAI virus was detected in Vietnam immediately after its initial detection in China in 2013[13]. Nguyen et al.[30] showed that in the period from 2014 to 2017, two predominant clades of H5 HPAI viruses, 2.3.2.1c and 2.3.4.4, evolved from homologous clade viruses endemicTable 1Closest related viruses and identification of amino acids deduction of A/chicken/Vietnam/AI-1606/2016 (H5N6) isolate involved in binding to human-type influenza receptor, enhancing antiviral drug resistance, and causing pathogenesis in mammals *Amino acid position, A alanine; D aspartic acid; E glutamic acid; G glycine; H histidine; I Isoleucine; K lysine; L leucine; M methionine; N asparagine; P proline; Q glutamine; R arginine; S serine; T threonine, V valine; Y tyrosine ...
Sites of live poultry trade and marketing are hot spots for avian influenza virus (AIV) transmission. We conducted active surveillance at a local live poultry market (LPM) in northern Vietnamese provinces in December 2016. Feces samples from the market were collected and tested for AIV. A new reassorted AIV strain was isolated from female chickens, named A/chicken/Vietnam/AI-1606/2016 (H5N6), and was found to belong to group C of clade 2.3.4.4 H5N6 highly pathogenic (HP) AIVs. The neuraminidase gene belongs to the reassortant B type. The viral genome also contained polymerase basic 2 and polymerase acidic, which were most closely related to domestic-duck-origin low pathogenic AIVs in Japan (H3N8) and Mongolia (H4N6). The other six genes were most closely related to poultry-origin H5N6 HP AIVs in Vietnam and had over 97% sequence identity with human AIV isolate A/Guangzhou/39715/2014 (H5N6). The new reassorted AIV isolate A/chicken/Vietnam/AI-1606/2016 (H5N6) identified in this study exemplifies AIVs reassortment and evolution through contact among wild birds, poultry farms, and LPMs. Therefore, active surveillance of AIVs is necessary to prevent potential threats to human and animal health.
... In addition, Ohkawara et al. [82] reported that H5 viruses in the same clades showed HA inhibition titers differing by 2-fold and 4-fold, and by 8-fold if belonging to different clades. In the present study, HA inhibition titers were consistent with those of previous studies, indicating antigenic differences between H5 viruses in clades 2.3.2.1c and 2.3.4.4 [83]. It also demonstrated that the antigenicity of the KNU18-91 isolate differed from that of H5 HPAIVs and LPAIV A/spotbilled duck/Korea/KNU SYG06/2006 (H5N3) by 32-fold and 16-fold, respectively. ...
Introduction:
The avian influenza (AI) virus causes a highly contagious disease which is common in wild and domestic birds and sporadic in humans. Mutations and genetic reassortments among the 8 negative-sense RNA segments of the viral genome alter its pathogenic potential, demanding well-targeted, active surveillance for infection control.
Methods:
Wild duck fecal samples were collected during the 2018 bird health annual surveillance in South Korea for tracking variations of the AI virus. One low-pathogenic avian influenza H5N3 reassortment virus (A/mallard duck/South Korea/KNU18-91/2018 [H5N3]) was isolated and genomically characterized by phylogenetic and molecular analyses in this study.
Results:
It was devoid of polybasic amino acids at the hemagglutinin (HA) cleavage site and exhibited a stalk region without deletion in the neuraminidase (NA) gene and NA inhibitor resistance-linked E/D627K/N and D701N marker mutations in the PB2 gene, suggesting its low-pathogenic AI. It showed a potential of a reassortment where only HA originated from the H5N3 poultry virus of China and other genes were derived from Mongolia. In phylogenetic analysis, HA was different from that of the isolate of H5N3 in Korea, 2015. In addition, this novel virus showed adaptation in Madin-Darby canine kidney cells, with 8.05 ± 0.14 log10 50% tissue culture infectious dose (TCID50) /mL at 36 h postinfection. However, it could not replicate in mice well, showing positive growth at 3 days postinfection (dpi) (2.1 ± 0.13 log10 TCID50/mL) but not at 6 dpi.
Conclusions:
The HA antigenic relationship of A/mallard duck/South Korea/KNU18-91/2018 (H5N3) showed differences toward one of the old low-pathogenic H5N3 viruses in Korea. These results indicated that a novel reassortment low-pathogenic avian influenza H5N3 subtype virus emerged in South Korea in 2018 via novel multiple reassortments with Eurasian viruses, rather than one of old Korean H5N3 strains.
... In this phylogenetic analysis, H5 HA genes were divided into two lineages: Eurasian and North American. The Eurasian lineage was clustered into two sub-lineages: Gs/Gd-like and non-Gs/ Gd [12]. All H5N3 isolates from migratory waterfowl in Mongolia in 2019 belonged to the non-Gs/Gd sub-lineage that clustered with H5N3 subtype viruses recently reported in Asia and were distinct from Gs/Gd-like viruses. ...
The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country.
... In [10,25]. Therefore, it is possible that new H5N6 viruses with 2.3.2.1c-original HA (similar to the Jiangxi strain) will be introduced to Vietnam and that reassortment activities may occur. ...
Vietnam is one of the countries most affected worldwide by the highly pathogenic avian influenza (HPAI) virus, which caused enormous economic loss and posed threats to public health. Over nearly two decades, with the antigenic changes in the diversified H5Ny viruses, the limited protective efficacy of the available vaccines was encountered. Therefore, it is necessary to approach a technology platform for the country to accelerate vaccine production that enables quick response to new influenza subtypes. This study utilized a powerful reverse genetics technique to successfully generate a recombinant H5N1 vaccine strain (designated as IBT-RG02) containing two surface proteins (haemagglutinin (HA) and neuraminidase (NA)) from the HPAI H5N1 (A/duck/Vietnam/HT2/2014(H5N1)) of the dominant clade 2.3.2.1c in Vietnam during 2012–2014. Importantly, the IBT-RG02 vaccine candidate has elicited high antibody titres in chickens (geometric mean titre (GMT) of 6.42 and 6.92, log2 on day 14 and day 28 p.i., respectively). To test the efficacy, immunized chickens were challenged with the circulating virulent strains. As results, there was a high protection rate of 91.6% chickens against the virulent A/DK/VN/Bacninh/NCVD-17A384/2017 of the same clade and a cross-protection of 83.3% against A/duck/TG/NAVET(3)/2013 virus of clade 1.1. Our promising results showed that we can independently master the reverse genetics technology for generation of highly immunogenic vaccine candidates, and henceforth, it is a timely manner to reformulate avian influenza virus vaccines against variable H5 clade HPAI viruses in Vietnam.
... Re-6 with 144NGS might have been effective against clade 2.3.2.1a, b, and c viruses not only due to antigenic similarity but also due to the restricted acquisition of additional 158NGS. The very low frequency of A(H5) viruses possessing both 144NGS and 158NGS (0.1%) may reflect the inferior competitiveness of such HAs in nature ( [10,52,53]. ...
Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A (A(H5N1)) viruses have evolved to clade 2.3.2.1a, b, and c; currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of the clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells, and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity.
Background
The geographic expansion and evolution of A/Goose/Guangdong/1/1996(H5N1) (Gs/GD) lineage H5Nx highly pathogenic avian influenza (HPAI) viruses since 1996 have raised awareness of enzootic circulation among migratory birds and the potential for intercontinental transport and spread. Recent Pacific- and Atlantic-route introductions of HPAI to North America were facilitated by avian migration through subarctic zones, specifically Alaska and Iceland. This study aimed to identify recent historic patterns of exposure to HPAI viruses among birds within and migrating through both regions and evaluate how geographic, demographic, and taxonomic differences contribute to exposure risk at two intercontinental staging locations.
Methods
During 2010–2019, blood samples were obtained from captured wild migratory seabirds and waterfowl in Alaska and Iceland. All live birds were released following completion of sampling. Sampling date, species, sampling location, and age class was documented for each bird, and sex was documented when possible. Lentiviral pseudoviruses that express the influenza hemagglutinin surface glycoprotein for H5Nx HPAI and H5 low-pathogenicity avian influenza (LPAI) were constructed for use in serological assays to screen for and quantify titers of antibodies against the latter viruses. Data were analyzed to compare a) categorical baseline ecological traits between Iceland and Alaska, and b) ecological traits between birds identified to be seropositive and suggestive/seronegative/fully cross-reactive birds to H5Nx HPAI in Iceland and Alaska. Factors associated with seroreactivity to H5Nx HPAI and H5 LPAI were assessed.
Results
The seroprevalence of HPAI among birds in both locations was 7.3% (112/1528). Findings reveal variability in seroprevalence by year, higher rates of exposure to H5 LPAI than H5Nx HPAI overall, and significantly more seropositive and suggestive exposure of birds to H5Nx HPAI in Alaska as compared to Iceland. Geographic, demographic, and taxonomic differences contribute to exposure risk between Alaska and Iceland. Most tested birds were immuno-naïve to HPAI in both locations, which suggests many migratory birds in the subarctic are susceptible to HPAI infection, demonstrating significant risk for intercontinental transmission between Asia, Europe, and North America.
Conclusions
Our findings provide further justification for increased viral and serosurveillance in Alaska and Iceland to monitor subarctic movements of migratory birds and intercontinental transmission dynamics of currently circulating and new strains of HPAI globally.
