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An overview of the epidemiology of avian influenza
Abstract
Only viruses of the Influenzavirus A genus have been isolated from birds and termed avian influenza [AI] viruses, but viruses with all 16 haemagglutinin [H1-H16] and all 9 neuraminidase [N1-N9] influenza A subtypes in the majority of possible combinations have been isolated from avian species. Influenza A viruses infecting poultry can be divided into two groups. The very virulent viruses causing highly pathogenic avian influenza [HPAI], with flock mortality as high as 100%. These viruses have been restricted to subtypes H5 and H7, although not all H5 and H7 viruses cause HPAI. All other viruses cause a milder, primarily respiratory, disease [LPAI], unless exacerbated. Until recently HPAI viruses were rarely isolated from wild birds, but for LPAI viruses extremely high isolation rates have been recorded in surveillance studies, with overall figures of about 11% for ducks and geese and around 2% for all other species. Influenza viruses may infect all types of domestic or captive birds in all areas of the world, the frequency with which primary infections occur in any type of bird usually depending on the degree of contact there is with feral birds. Secondary spread is usually associated with human involvement, either by bird or bird product movement or by transferring infective faeces from infected to susceptible birds, but potentially wild birds could be involved. In recent years there have been costly outbreaks of HPAI in poultry in Italy, The Netherlands and Canada and in each millions of birds were slaughtered to bring the outbreaks under control. Since the 1990s AI infections due to two subtypes have been widespread in poultry across a large area of the World. LPAI H9N2 appears to have spread across the whole of Asia in that time and has become endemic in poultry in many of the affected countries. However, these outbreaks have tended to have been overshadowed by the H5N1 HPAI virus, initially isolated in China, that has now spread in poultry and/or wild birds throughout Asia and into Europe and Africa, resulting in the death or culling of hundreds of millions of poultry and posing a significant zoonosis threat.
... Avian influenza, or bird flu, is a viral infection that largely affects birds, though certain strains can also infect humans and other animals [1,2]. It is caused by the Alphainfluenzavirus influenzae (influenza A) virus, which circulates naturally among wild aquatic birds (e.g., ducks, geese, swans) [3]. While many avian influenza viruses cause slight or no symptoms in birds, certain strains can be highly pathogenic, leading to severe illness and death [1]. ...
... Various influenza viruses are maintained within wild bird populations, with over 1100 species from 15 orders identified as carriers [3]. The first isolation of avian influenza virus in wild birds occurred in 1961 from Common Terns (Sterna hirundo) in South Africa. ...
... Transmission among wild birds occurs primarily through direct and indirect contact, especially in environments where birds congregate, such as wetlands, lakes, and coastal areas (Figure 2) [4,12]. The virus is commonly spread via contaminated water, as infected birds shed the virus in their faeces, saliva, and nasal secretions [3,13]. Waterfowl, shorebirds, and seabirds are particularly susceptible due to their close association with aquatic habitats, where the virus can stay viable for extended periods, especially in cold water or frozen conditions [8,14]. ...
Avian influenza, also known as bird flu, significantly threatens wild bird populations and global biodiversity. As wild birds are natural reservoirs for various strains of the influenza virus, they have a crucial role in the epidemiology of the disease, which has profound implications for both wildlife conservation and public health. The emergence and dispersion of highly pathogenic avian influenza strains, particularly H5N1, have resulted in large-scale mortality events in wild bird populations, disrupting ecosystems and threatening endangered species. The conservation of wild birds in the context of avian flu involves several critical actions, including surveillance, rapid response to outbreaks, habitat management, and minimizing human-wildlife interactions that facilitate virus transmission. Studying avian influenza's impact on wild bird populations is crucial due to its dual importance in wildlife conservation and public health. Wild birds, as natural reservoirs of the virus, play a central role in its spread, with highly pathogenic strains like H5N1 causing devastating mortality events that disrupt ecosystems and endanger species. Effective management, including monitoring, rapid outbreak response, and habitat protection, is essential to mitigate these effects. Collaboration among experts is vital to protect biodiversity, sustain ecological balance, and reduce risks to human health, ensuring the long-term survival of wild bird populations.
... AIVs are classified as low-or high-pathogenicity avian influenza viruses based on clinical signs in birds [11]. Two aspects involving HA are considered key virulence factors: (i) the differential HA binding affinity to α2-3 and α2-6 sialic acid receptors, and (ii) the presence of a polybasic cleavage site (PBCS). ...
... PBCSs have been so extensively found in H5N1 that the presence of a PBCS often dictates the use of the term and association to HPAI viruses. This classification is restricted to the H5 and H7 subtypes [12], and viruses are often classified as low-or high-pathogenicity avian influenza viruses based on the absence or presence of this PBCS (LPAI or HPAI, respectively) [11]. ...
... Over the last 20 years, non-human mammals have also been infected, with recent and unusual mass mortality events, while human infections have been sporadic and restricted to bird contacts. Before 2003, HPAI H5N1 virus isolates were also reported: the first reports were in chickens in Scotland in 1959 from a small farm; in turkeys in England in 1991, with about eight thousand poultry involved; and in chickens in Hong Kong in 1997, involving about three million poultry [11]. In 1997, the virus detected in Hong Kong jumped to humans, with 18 cases (six fatal) reported. ...
The prevalence of the highly pathogenic avian influenza virus H5N1 in wild birds that migrate all over the world has resulted in the dissemination of this virus across Asia, Europe, Africa, North and South America, the Arctic continent, and Antarctica. So far, H5N1 clade 2.3.4.4.b has reached an almost global distribution, with the exception of Australia and New Zealand for autochthonous cases. H5N1 clade 2.3.4.4.b, derived from the broad-host-range A/Goose/Guangdong/1/96 (H5N1) lineage, has evolved, adapted, and spread to species other than birds, with potential mammal-to-mammal transmission. Many public health agencies consider H5N1 influenza a real pandemic threat. In this sense, we analyzed H5N1 hemagglutinin sequences from recent outbreaks in animals, clinical samples, antigenic prototypes of candidate vaccine viruses, and licensed human vaccines for H5N1 with the aim of shedding light on the development of an H5N1 vaccine suitable for a pandemic response, should one occur in the near future.
... The influenza A virus subtypes can be differentiated by the H and N antigens on the virus surface [10]. Each influenza virus expresses one H antigen and one N antigen, which can appear in any combination [10]. ...
... The influenza A virus subtypes can be differentiated by the H and N antigens on the virus surface [10]. Each influenza virus expresses one H antigen and one N antigen, which can appear in any combination [10]. Currently, 16 different H subtypes (H1-H16) and 9 N subtypes (N1-N9) have been identified [10]. ...
... Each influenza virus expresses one H antigen and one N antigen, which can appear in any combination [10]. Currently, 16 different H subtypes (H1-H16) and 9 N subtypes (N1-N9) have been identified [10]. The influenza B viruses are classified into two lineages, Victoria and Yamagata, based on the genetic and antigenic differences in H and N [11]. ...
Avian Influenza viruses (AIVs) has posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, and pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from the previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.
... The target population included backyard farmers and household members from BPS breeding poultry and/or swine in a radius of 5 km from wetlands located throughout Chile: (i) Lluta River estuary, in Arica and Parinacota region; (ii); Batuco wetland, in Metropolitan region; (iii) El Yali National Reserve, in Valparaiso region; (iv) Itata River estuary, in Ñuble region and (v) Mocha Island, in Bío-Bío region ( Figure 1). Therefore, the BPS in the selected sites represents a particular interface where domestic animals, wildlife and human interact, posing a considerable risk of circulation of IAV in backyard animals (Alexander 2007). In each study area, BPS were selected through a convenient sampling method. ...
... This is particularly important considering that the target population of this study was BPS located in the proximity of wetlands of high concentration of wild birds. The introduction of IAV in poultry is the result of the interaction with the natural reservoirs of the virus, represented by wild birds (Alexander 2007;Olsen et al. 2006). Recently, a long-term longitudinal study performed in multiple wetlands in central Chile has revealed ranging IAV prevalence in wild aquatic birds among seasons, with a significant increase during summer (~9%) and fall (~4%) (Ruiz et al. 2021). ...
Aim:
Backyard production systems (BPS) represent an interface of contact between people, domestic and wild animals. Studies conducted in Chile during the last decade have provided extensive evidence of influenza A virus (IAV) circulation in backyard poultry and swine. The aim of this study was to investigate exposure practices of humans to animal-origin IAV within backyards.
Methods and results:
Backyard farmers and household members of a total of 101 BPS in the proximity of wetlands located throughout Chile were interviewed between 2021 and 2022. Data were collected on the nature of human-animal contacts through participation in productive activities conducted within backyards, which was used to estimate participants' exposure risk to animal-origin IAV. Additionally, RT-qPCR and serologic IAV active surveillance was carried out in backyard animals. Multilinear regression was used to identify factors associated with exposure risk. Overall, IAV prevalence was 10.1% (95% CI: 4.7%-15.5%) and seroprevalence was 43.5% (95% CI: 29.7%-54.2%), both at the BPS level. Of 180 interviewees, 86% reported participating regularly in poultry or swine exposure activities within the backyard. A greater participation of male participants was observed when evaluating swine exposure activities, while female participation was greater for some activities related to poultry handling. Handwashing was a very extended hygiene practice; however, the use of personal protective equipment was uncommon. Different factors related to participants, households and backyards were associated with an increased exposure risk of participants to animal-origin IAV: (i) older age, (ii) less years of education, (iii) no off-farm work, (iv) greater backyard production value and (v) greater household consumption of backyard products.
Conclusion:
These results indicate the circulation of IAV in BPS and the frequent human-animal contact at this interface, highlighting the need for awareness campaigns and educational programmes aimed at backyard farmers on prevention and biosecurity measures in the management of backyard animals.
... Direct or indirect contact is recognized as the main source of avian IAV transmission to domestic poultry [5]. In open-door areas on a free-range poultry farm, wild waterfowl can access feed on the ground, facilitating direct contact with domestic poultry. ...
... In open-door areas on a free-range poultry farm, wild waterfowl can access feed on the ground, facilitating direct contact with domestic poultry. Risk factors for indirect contact include wind-borne spread, food and water contamination, movement of vehicles and people, and virus-contaminated fomites [5][6][7]. In addition, other intermediate species, including rodents, may play a role in virus spread to domestic poultry [8]. ...
Avian influenza A viruses (IAVs) present significant threats to both animal and human health through their potential for cross-species transmission and global spread. Clade 2.3.4.4 H5Nx highly pathogenic avian IAVs initially emerged in East Asia between 2013 and 2014. Since then, they have spread to Europe, Africa, and America via migratory bird flyways. However, beyond viral transmission primarily facilitated by migratory birds, the potential involvement of other intermediate factors for virus transmission remains poorly investigated. This study aimed to investigate the role of wild rodents as intermediary hosts in the ecology of avian IAVs in Gyeonggi province, South Korea. By capturing and analyzing 189 wild rodents near poultry farms and migratory bird habitats in 2013 and 2014 and employing serological assays and virus isolation techniques, we found no evidence of IAV infection among these populations. Our results suggest that wild rodents may not significantly contribute to the transmission dynamics of IAVs within these regions.
... Avian influenza strains in these birds are the Low-Pathogenicity Avian Influenza (LPAI) and High-Pathogenicity Avian Influenza (HPAI). 10 LPAI strains are more prevalent in birds and typically result in no symptoms, or if any, only mild illness. In humans, both LPAI and HPAI strains have the potential to trigger severe avian influenza outbreaks, with HPAI strains doing so more often. ...
... In humans, both LPAI and HPAI strains have the potential to trigger severe avian influenza outbreaks, with HPAI strains doing so more often. 10 The HPAI virus (H5N1) outbreak that emerged in the Middle East among human populations between 1997 and 2007 had severe consequences, causing respiratory complications and, in some cases, fatalities. 11 It spreads through direct contact, contaminated environments, and respiratory droplets. ...
The World Organization for Animal Health defines Avian Influenza Virus as a highly infectious disease caused by diverse subtypes that continue to evolve rapidly, impacting poultry species, pet birds, wild birds, non-human mammals, and occasionally humans. The effects of Avian influenza viruses have been recognised as a precursor for serious health concerns among affected birds, poultry, and human populations in the Middle East. Furthermore, low and high pathogenic avian influenza viruses lead to respiratory illness with varying severity, depending on the virus subtype (e.g., H5, H7, H9, etc.). Possible future outbreaks and endemics of newly emerging subtypes are expected to occur, as many studies have reported the emergence of novel mutations and viral subtypes. However, proper surveillance programs and biosecurity applications should be developed, and countries with incapacitated defences against such outbreaks should be encouraged to undergo complete reinstation and reinforcement in their health and research sectors. Public education regarding biosafety and virus prevention is necessary to ensure minimal spread of avian influenza endemic.
... Therefore, the specific mechanism(s) allowing initial introduction events [2] remain unclear. One hypothesized method by which AIV could enter commercial poultry facilities involves human-mediated transmission, where personnel entering barns transport virus on their shoes, clothes, or skin or on equipment being brought into the barn [14][15][16]. Similarly, virus could be entering facilities via contaminated feed or water [14][15][16]. ...
... One hypothesized method by which AIV could enter commercial poultry facilities involves human-mediated transmission, where personnel entering barns transport virus on their shoes, clothes, or skin or on equipment being brought into the barn [14][15][16]. Similarly, virus could be entering facilities via contaminated feed or water [14][15][16]. An additional potential method of viral introduction is via aerosolized virus entering through the barn's ventilation [17], though this has previously been discussed primarily in the context of farm-to-farm transmission [18,19]. ...
While the recent incursion of highly pathogenic avian influenza into North America has resulted in notable losses to the commercial poultry industry, the mechanism by which virus enters commercial poultry houses is still not understood. One theorized mechanism is that waterfowl shed virus into the environment surrounding poultry farms, such as into retention ponds, and is then transmitted into poultry houses via bridge species. Little is known about if and when wild waterfowl use these retention ponds, leading to uncertainty regarding the potential significance of this interface. To quantify the use of retention ponds on commercial poultry farms by wild waterfowl, we surveyed 12 such ponds across Somerset and Dorchester counties, Maryland, USA. This region was chosen due to the high level of poultry production and its importance for migratory waterfowl. Surveys consisted of recording waterfowl visible on the retention ponds from public roadways at least once per week from 20 September 2022-31 March 2023. Throughout the course of this study, we observed a total of nine species of waterfowl using retention ponds on commercial poultry farms at nine of 12 sites. The number of waterfowl observed at retention ponds varied notably throughout the course of our survey period, with values generally following trends of fall migration within each species indicating that resident birds were not the only individuals to utilize these habitats. Additionally, waterfowl use was highest at sites with little vegetation immediately surrounding the pond, and lowest when ponds were surrounded by trees. Our data suggest that retention ponds on commercial poultry farms present a notable interface for waterfowl to introduce avian influenza viruses to farm sites. However, additional testing and surveys could provide further insight into whether it may be possible to reduce the use of these habitats by wild waterfowl through vegetative management as preliminarily reported here.
... Veterinarians, infectious disease specialists, and historians have documented "fowl plague" on chicken farms since the nineteenth century [16][17][18][19][20][21]. From 1878 through 1955, fowl plaque was a high-mortality poultry disease in many countries. ...
Beginning in 2005, Qinghai Lake on the Tibetan Plateau was the scene of the unprecedented appearance of avian influenza among migratory birds. These were significant events in the subsequent global spread of the virus to poultry (and occasionally humans) in many new countries on three continents. Events at Qinghai sparked energetic debates about the role of migratory birds in spreading influenza viruses among domestic and wild birds. In turn, this led to cross-disciplinary research that highlighted the interconnections of environment, wildlife, and human activities. Factors in the Qinghai case study (Qinghai) include the vast permafrost landscape of the Tibetan Plateau, the ecology of wild geese that migrate over the Himalayas, a high-altitude railway (the “permafrost rooster”) that traverses the Tibetan Plateau, and an avian virus (H5N1). This chapter considers multiple factors: the ecology of migratory birds, agricultural practices that mix wild and domestic birds, climate warming, and factory poultry farming. As a place at the crossroads of interconnected global phenomena such as avian influenza and climate change, the Qinghai case study provides a lens to envision the unintended consequences of natural and human forces over the coming decades.
... First, an HPAI virus termed HPAI has been identified as a lethal virus-producing bird plague [48]. This group was restricted to H5 and H7 rats, and the mortality rate was approximately 100% [49]. Second, another virus known as low pathogenic AI (LPAI) causes mild respiratory sickness [50]. ...
One of the worst zoonotic illnesses, avian influenza (AI), or commonly referred to as bird flu, is caused by viruses belonging to the genus Influenza viruses, which are members of the Orthomyxoviridae family. The harmful effects of AI illness can affect both human and animal health and cause financial losses. Globally, the AI virus lacks political purpose and is not limited by geographical limits. It has been isolated from poultry, wild birds, and captive birds in Asia, North America, Europe, Australia, and South America. Their virulence is divided into highly pathogenic AI (HPAI) and low pathogenic AI (LPAI). The AI virus can also be diagnosed in a laboratory setting using molecular tests like real-time polymerase chain reaction or serological tests like the hemagglutinin inhibition test, agar gel immunodiffusion, antigen detection enzyme-linked immunosorbent assay, and other immunoassays. The type of AI virus and host species determines the clinical manifestations, severity, and fatality rates of AI. Human infection with AI viruses typically results from direct transmission from infected birds to humans. AI outbreaks in domestic and wild birds are uncommon; however, an infection can pose a significant threat to public, veterinary, and medical health. Successful vaccination reduces the probability of AI H5N1 virus infection in meat and other poultry products and prevents systemic infection in chickens. This review will provide information that can be used as a reference for recognizing the dangers of AI and for preventing and controlling the disease, considering its potential to become a serious pandemic outbreak. Keywords: avian influenza, disease, human health, poultry, virus.
... Most outbreaks of H5 avian influenza A viruses (AIVs) have been geographically confined and successfully eradicated through the implementation of national disease control strategies [2,3]. Nevertheless, several Gs/GD lineage H5Nx viruses have been spread by migratory birds, which has led to the emergence of the global highly pathogenic avian influenza viruses (HPAIVs) outbreak, and viruses that belong to only clade 2.2, clade 2.3.2, or clade 2.3.4.4 have been maintained through wild birds [4][5][6]. In particular, clade 2.3.4.4 viruses have emerged globally since 2014, and they have evolved into eight subgroups (2.3.4.4a-2.3.4.4h) according to the phylogenetic classification by the World Health Organization (WHO) [5,7,8]. ...
The emergence and evolution of avian influenza A viruses (AIVs) pose significant challenges to both public health and animal husbandry worldwide. Here, we characterized a novel reassortant highly pathogenic avian influenza virus (HPAIV), clade 2.3.4.4b H5N6, that was isolated from a mandarin duck in South Korea in December 2023. Phylogenetic and molecular analyses show that the hemagglutinin (HA) gene of the 23-JBN-F12-36/H5N6 virus clustered with HPAIV clade 2.3.4.4b H5N1 viruses, which were circulating in South Korea and Japan in 2022–2023. The M and polymerase acidic (PA) genes also revealed a close association with the HPAIV clade 2.3.4.4b H5N1 AIV that was identified previously in South Korea during November 2022. Notably, the neuraminidase (NA) gene of the 23-JBN-F12-36/H5N6 virus was estimated to have its origins in the HPAIV clade 2.3.4.4h H5N6 prevalent in poultry in China, and it is clustered with the AIVs that are associated with human infection cases. Taken together, these results show that the virus has been produced by reassortment with H5N1 HPAIV, which is prevalent in wild birds; H5N6 HPAIV, which is circulated in poultry in China; and the internal genes of low pathogenic avian influenza viruses (LPAIVs). In light of the reassortment of HPAIVs circulating in existing wild birds and HPAIVs circulating in poultry in China within the 2.3.4.4b H5Nx clade, it is imperative to strengthen active surveillance across wild bird populations, poultry farms, and live poultry markets, and to inform for the effective design of improved prevention and control strategies.
... While improved diagnostic techniques and reporting infrastructure have increased our ability to detect HPAIV outbreaks, the increase in their frequency and intensity is in part due to changes in agricultural practices that have led to increased densities of poultry populations, and their proximity to wild birds [9,10]. Despite efforts to control the spread of HPAIVs (e.g. ...
Avian influenza viruses (AIVs) regularly circulate between wild and domestic bird populations. Following several high-profile outbreaks, highly pathogenic AIVs (HPAIV) with zoonotic potential have been the subject of increasing attention. While we know that HPAIV is transmitted between domestic birds, wildlife, and the environment, little is known about persistence and spillover/back at these interfaces. We integrated the test results of samples collected on and around an infected domestic poultry premise (IP) where H5N1 HPAIV was confirmed in a flock of poultry in 2022 in Southern Ontario, Canada to explore the transmission cycle of AIVs in wildlife and the environment. We sampled a captive flock of Mallards (Anas platyrhynchos) that resided on site, sediment samples collected from water bodies on site, and examined samples collected through surveillance within a 100 km radius of the IP from live wild ducks and sick and dead wildlife. We found serologic evidence of H5 exposure in the captive mallards that resided on site despite no evidence of morbidity or mortality in these birds and no PCR positive detections from samples collected at two different timepoints. Genetic material from the same H5N1 HPAIV subtype circulating in the domestic birds and from low pathogenicity avian influenza viruses were detected in wetlands on site. The results of live and sick and dead surveillance conducted within a 100 km radius confirmed that the virus was circulating in wildlife before and after IP confirmation. These results suggest that biosecurity remains the most critical aspect of minimising spillover/back risk in a virus that has been shown to circulate in asymptomatic wild birds and persist in the surrounding environment.
... Avian influenza virus (AIV) is one of the most well-known pathogens, and its constant circulation has a significant impact on public health and the global economy. AIVs are segmented, single-stranded RNA viruses of the Orthomyxoviridae family and are highly variable [1]. The genetic and antigenic variability of surface glycoproteins HA and NA is most pronounced. ...
In the winter of 2023/2024, the mass death of swans was observed on Lake Karakol on the eastern coast of the Caspian Sea. From 21 December 2023 to 25 January 2024, 1132 swan corpses (Cygnus olor, Cygnus cygnus) were collected and disposed of on the coast by veterinary services and ecologists. Biological samples were collected from 18 birds for analysis at different dates of the epizootic. It was found that the influenza outbreak was associated with a high concentration of migrating birds at Lake Karakol as a result of a sharp cold snap in the northern regions. At different dates of the epizootic, three avian influenza A/H5N1 viruses of clade 2.3.4.4.b were isolated from dead birds and identified as highly pathogenic viruses (HPAIs) based on the amino acid sequence of the hemagglutinin multi-base proteolytic cleavage site (PLREKRRRKR/G). A phylogenetic analysis showed that the viruses isolated from the swans had reassortations in the PB2, PB1, and NP genes between highly pathogenic (HP) and low-pathogenic (LP) avian influenza viruses. Avian influenza viruses A/Cygnus cygnus/Karakol lake/01/2024(H5N1) and A/Mute swan/Karakol lake/02/2024(H5N1) isolated on 10 January 2024 received PB2, PB1, and NP from LPAIV, while A/Mute swan/Mangystau/9809/2023(H5N1) isolated on 26 December 2023 received PB1 and NP from LPAIV, indicating that the H5N1 viruses in this study are new reassortants. All viruses showed amino acid substitutions in the PB2, PB1, NP, and NS1 segments, which are critical for enhanced virulence or adaptation in mammals. An analysis of the genomes of the isolated viruses showed that bird deaths during different periods of the epizootic were caused by different reassortant viruses. Kazakhstan is located at the crossroads of several migratory routes of migratory birds, and the possible participation of wild birds in the introduction of various pathogens into the regions of Kazakhstan requires further study.
... Avian influenza (AI) is a major zoonotic viral disease that causes significant adverse impacts on poultry production, the global trade, and public health (Capua et al., 2002;Alexander DJ, 2007). Despite decades of research and control efforts, the incidences and severity of AI outbreaks have not been alleviated but rather increased (CDC, 2017;USDA, 2017). ...
... Avian influenza viruses (AIVs) are responsible for major economic losses to the poultry sector and have a detrimental impact on the health and welfare of chickens (1). AIVs can also transmit between species, causing a disease burden in other livestock, wild animals, and humans, emphasising the importance of infection control in poultry (2). ...
Avian influenza viruses (AIVs) are a major economic burden to the poultry industry and pose serious zoonotic risks, with human infections being reported every year. To date, the vaccination of birds remains the most important method for the prevention and control of AIV outbreaks. Most national vaccination strategies against AIV infection use whole virus-inactivated vaccines, which predominantly trigger a systemic antibody-mediated immune response. There are currently no studies that have examined the antibody repertoire of birds that were infected with and/or vaccinated against AIV. To this end, we evaluate the changes in the H9N2-specific IgM and IgY repertoires in chickens subjected to vaccination(s) and/or infectious challenge. We show that a large proportion of the IgM and IgY clones were shared across multiple individuals, and these public clonal responses are dependent on both the immunisation status of the birds and the specific tissue that was examined. Furthermore, the analysis revealed specific clonal expansions that are restricted to particular H9N2 immunisation regimes. These results indicate that both the nature and number of immunisations are important drivers of the antibody responses and repertoire profiles in chickens following H9N2 antigenic stimulation. We discuss how the repertoire biology of avian B-cell responses may affect the success of AIV vaccination in chickens, in particular the implications of public versus private clonal selection.
... LPAI A(H9N2) virus has been circulating in poultry farms in Ghana since 2017 (WHO, online-c). A(H9N2) viruses have become endemic in poultry (mainly in chicken) since the mid-1990s in many countries in Asia and the Middle East (Alexander, 2007;El Sayes et al., 2022) and since towards the end of the 2010s in Africa (Fusade-Boyer et al., 2021). This circulation of A(H9N2) strains in domestic birds can be linked to zoonotic infections. ...
Between 15 June and 20 September 2024, 75 highly pathogenic avian influenza (HPAI) A(H5) and A(H7) virus detections were reported in domestic (16) and wild (59) birds across 11 countries in Europe. Although the overall number of detections in Europe continued to be low compared to previous epidemiological years, an increase in cases along the Atlantic, North Sea and Baltic coasts was notable, particularly an increase in the detection of HPAI viruses in colony‐breeding seabirds. Besides EA‐2022‐BB and other circulating genotypes, these detections also included EA‐2023‐DT, a new genotype that may transmit more efficiently among gulls. In Germany, HPAI A(H7N5) virus emerged in a poultry establishment near the border with the Netherlands. No new HPAI virus detections in mammals were reported in Europe during this period, but the number of reportedly affected dairy cattle establishments in the United States of America (USA) rose to >230 in 14 states, and HPAI virus was identified in three new mammal species. Between 21 June and 20 September 2024, 19 new human cases with avian influenza virus infection were reported from the USA (six A(H5N1) cases and five A(H5) cases), Cambodia (five A(H5N1) cases, including one fatal), China (one fatal A(H5N6) case and one A(H9N2) case), and Ghana (one A(H9N2) case). Most of the human cases (90%, n = 17/19) had reported exposure to poultry, live poultry markets, or dairy cattle prior to avian influenza virus detection or onset of illness. Human infections with avian influenza viruses remain rare and no evidence of human‐to‐human transmission has been documented in the reporting period. The risk of infection with currently circulating avian A(H5) influenza viruses of clade 2.3.4.4b in Europe remains low for the general public in the European Union/European Economic Area (EU/EEA). The risk of infection remains low‐to‐moderate for those occupationally or otherwise exposed to infected animals or contaminated environments.
... Influenza viruses in natural ecosystems spread through droppings from water birds and contaminated objects, favouring strains with low harm. Certain strains like H5 or H7 can become highly dangerous in poultry farms [6]. ...
Avian influenza viruses, particularly H5N1, H7N9, and H9N2, pose significant threats to avian and human populations through zoonotic transmission, as they have potential to change their genetic material through mutations. Symptoms of Avian Influenza ranges from mild to severe, mainly respiratory problems in both and muscle aches, fatigue in humans. This review highlights the molecular mechanisms by which the virus infects host cells, emphasizing the roles of hemagglutinin (HA) and neuraminidase (NA) in viral entry and release. Biochemical processes involved in viral replication, immune responses, and cytokine production are discussed, with a detailed examination of how antiviral drugs like neuraminidase and polymerase inhibitors disrupt these processes. Outbreak of AIV can cause mass culling results in massive economic loss, trade disruptions, and consumer reductions. The review also addresses the challenges posed by antiviral resistance and outlines novel therapeutic strategies, including combination therapies, vaccine advancements, and host-directed treatments. With an interdisciplinary "One Health" approach, this paper underscores the need for enhanced biosecurity, international cooperation, and continued research to mitigate the global impact of avian influenza.
... 9 Clearly, the longer the circulation of LPAI, the greater the probability of mutation. 10 The primary transmission route for avian influenza viruses involves direct contact between animals, although transmission can also occur through intermediate hosts such as pigs and, less frequently, domestic animals, including dogs and cats. These intermediary hosts facilitate viral transmission to the human sphere ( Figure 1). ...
Avian influenza viruses pose a great challenge to both animal and human health. This viral disease, mainly affecting chickens and birds, poses a substantial zoonotic threat, particularly with the highly pathogenic avian influenza strain. The avian population is a key vector for viral transmission and fosters genetic changes and reassortment events that amplify the infectivity besides broadening the spectrum of host species. Infected animals shed viral particles into the environment, contributing to the widespread dissemination of the viral disease and perpetuating the persistence of viral strains. Given these factors, it is imperative to strengthen monitoring and prevention measures to curb the spread of the virus. Implementing vaccination and testing programs within the animal population, along with stringent biosecurity measures in agricultural environments, including adequate hygiene practices, controlled access to farms, and the separation of different animal species, could effectively mitigate the prevalence of circulating viruses. The measures not only reduce the risk of environmental spread but also mitigate the risk of viral transmission to humans through the One Health approach.
... Although waterfowls and shorebirds are well known as the natural reservoirs of AIVs, these viruses have also established themselves in domestic poultry populations [5,8]. Based on their pathogenicity in chickens, AIVs were categorized into highly pathogenic avian in uenza viruses (HPAIVs) and low pathogenic avian in uenza viruses (LPAIVs) by the World Organization for Animal Health (WOAH) [9]. While HPAIVs, primarily H5 and H7 subtypes, pose severe threats to poultry and public health, LPAIVs often cause mild or asymptomatic infections. ...
The H3 subtype of avian influenza virus (AIV) stands out as one of the most prevalent subtypes, posing a significant threat to public health, and a novel triple-reassortant H3N3 AIV, designated A/chicken/China/16/2023 (H3N3), was isolated from a chicken in northern China. The complete genome of the isolate was determined using next-generation sequencing, and the AIV-like particles were confirmed via transmission electron microscopy. Phylogenetic analyses revealed that eight genes of the H3N3 isolate clustered within the Eurasian lineage of AIVs, indicating the novel H3N3 isolate has various constellations and was generated by complex reassortment events involving H3N8, H9N2, and H10N3 subtype influenza viruses. Strikingly, the HA gene of the H3N3 isolate exhibited the closest evolutionary relationships to a human-derived H3N8 influenza virus, posing a potential threat to public health. Additionally, the presence of Q226 and T228 in the HA protein suggests the H3N3 virus preferentially binds to α-2,3-linked sialic acid receptors. While the HA cleavage site motif (PEKQTR/GIF) and the absence of E627K and D701N mutations in PB2 protein classify the virus as a characteristic low pathogenicity AIV. However, several mutations in internal genes raise concerns about potential increases in viral resistance, virulence, and transmission in mammalian hosts. Overall, this study provides valuable insights into the molecular and genetic characterization of the emerging triple-reassortant H3N3 AIVs, and continued surveillance of domestic poultry is essential for monitoring the H3N3 subtype evolution and potential spread.
... The presence of multiple strains in viruses that cause diseases such as COVID-19 [1,2], flu [3], bird flu [4], dengue fever [5], and numerous others presents significant challenges in implementing effective measures to curb transmission. These challenges arise because newly emerging variants of these viruses consistently spark disease outbreaks, resulting in severe illness, loss of life, economic burdens, and social disruption globally [6,7]. ...
In this paper, we study optimal control solutions using a two-strain SARS-CoV-2 deterministic epidemic model characterized by standard incidence, alongside a two-strain stochastic model incorporating a random transmission rate. We present proofs demonstrating the existence, uniqueness, and boundedness of a positive solution for any positive initial value for both models. An algorithm for simulating the ensemble average optimal control solution is introduced and its realism is compared to both stochastic and deterministic solutions. Additionally, we include graphical representations to illustrate the dynamics and outcomes of our models. Our findings suggest that ensemble average optimal control simulations may offer enhanced visualization and realism compared to both stochastic and deterministic solutions.
... Antigenically classified based on their hemagglutinin (HA) and neuraminidase (NA) spike proteins into 18 HA and 11 NA variants (Davis, 2014;Fiala et al., 2018;Naguib et al., 2019). Highly pathogenic avian influenza viruses (HPAIVs), particularly subtypes H5 and H7, pose significant threats to poultry due to their high mortality rates and zoonotic potential (Alexander, 2007;Bialy and Shelton, 2020). Mortality rates in infected poultry flocks can reach 100%, affecting economic and food security (Perkins and Swain, 2003). ...
... This type of known or unknown vulnerability demonstrates the importance of infectious livestock diseases in global food security (38)(39)(40)(41)(42)(43). More specifically, and as aforementioned, the emergence of new pathogenic variants or the re-emergence of old infections and NIDs in the animal industry has devastated national flocks, as has occurred with strains of highly pathogenic avian influenza and others (7,(44)(45)(46)(47)(48)(49). ...
... Avian influenza (AI) is a contagious viral disease to which nearly all poultry species are susceptible, including chickens, ducks, geese, turkeys, pheasants, guinea fowl, quail, and partridges, but also mammals and carnivores 7. The most highly pathogenic subtypes of the AI virus cause severe Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. 2 disease symptoms (nasal and eye discharge, coughing, dyspnea, severe drowsiness, and diarrhea) and can be responsible for a mortality rate of up to 100% in infected poultry flocks [1,3,6]. Captive bird flocks can get contaminated with the AI virus through direct contact with contaminated wild birds, by consuming feed and water contaminated with the feces of wild birds, or by indirect transmission through human activity [7][8][9]. ...
Competent authorities of many countries, including Belgium, impose control measures (preventing wild bird access to feeders and water facilities, indoor confinement of captive birds, or fencing off outdoor ranges with nets) to professional and non-professional keepers of birds to prevent the spread of avian influenza (AI). Flemish laying hen farmers (FAR, n = 33) and private keepers of captive birds (PRI, n = 263) were surveyed about their opinion on, and compliance with, AI-measures legally imposed during the most recent high-risk period before this survey in 2021. Participants answered questions on a 5-point Likert scale (1 = the worst, 3 = neutral, and 5 = the best). FAR indicated better compliance with the AI-measures compared to PRI, except for confinement with nets. PRI and FAR perceived the level of compliance with AI-measures by other private bird keepers to be lower compared to themselves. FAR regarded the AI-measures as more effective than PRI. To prevent the spread of AI more effectively, national authorities could focus on information campaigns explaining to private bird keepers, in particular, the need for the various control measures that they impose, implement alternative control measures that have broader support or implement stricter enforcement of the control measures.
... It has been well documented that different avian influenza virus strains vary with regard to differential risks, even within subtype. Of particular note are the H5 and H7 subtypes (defined by the hemagglutinin surface protein) which have the potential to mutate and become highly pathogenic after spilling over into domestic poultry 56 . As such, we developed an additional pair of models focused on these two agriculturally important AIV subtypes. ...
The wild to domestic bird interface is an important nexus for emergence and transmission of highly pathogenic avian influenza (HPAI) viruses. Although the recent incursion of HPAI H5N1 Clade 2.3.4.4b into North America calls for emergency response and planning given the unprecedented scale, readily available data-driven models are lacking. Here, we provide high resolution spatial and temporal transmission risk models for the contiguous United States. Considering virus host ecology, we included weekly species-level wild waterfowl (Anatidae) abundance and endemic low pathogenic avian influenza virus prevalence metrics in combination with number of poultry farms per commodity type and relative biosecurity risks at two spatial scales: 3 km and county-level. Spillover risk varied across the annual cycle of waterfowl migration and some locations exhibited persistent risk throughout the year given higher poultry production. Validation using wild bird introduction events identified by phylogenetic analysis from 2022 to 2023 HPAI poultry outbreaks indicate strong model performance. The modular nature of our approach lends itself to building upon updated datasets under evolving conditions, testing hypothetical scenarios, or customizing results with proprietary data. This research demonstrates an adaptive approach for developing models to inform preparedness and response as novel outbreaks occur, viruses evolve, and additional data become available.
... Avian influenza viruses (AIVs) are classified into subtypes according to the external viral glycoproteins, namely the haemagglutinin (HA; H1-H16) and neuraminidase (NA; N1-N9) [1]. The H5 and H7 AIV subtypes are notifiable avian disease agents [2,3], and can mutate from the low pathogenicity (LP)AIV to the corresponding high pathogenicity (HP)AIV, with the latter causing high morbidity and mortality in poultry. ...
High pathogenicity avian influenza viruses (HPAIVs) cause high morbidity and mortality in poultry species. HPAIV prevalence means high numbers of infected wild birds could lead to spill over events for farmed poultry. How these pathogens survive in the environment is important for disease maintenance and potential dissemination. We evaluated the temperature-associated survival kinetics for five clade 2.3.4.4 H5Nx HPAIVs (UK field strains between 2014 and 2021) incubated at up to three temperatures for up to ten weeks. The selected temperatures represented northern European winter (4 °C) and summer (20 °C); and a southern European summer temperature (30 °C). For each clade 2.3.4.4 HPAIV, the time in days to reduce the viral infectivity by 90% at temperature T was established (DT), showing that a lower incubation temperature prolonged virus survival (stability), where DT ranged from days to weeks. The fastest loss of viral infectivity was observed at 30 °C. Extrapolation of the graphical DT plots to the x-axis intercept provided the corresponding time to extinction for viral decay. Statistical tests of the difference between the DT values and extinction times of each clade 2.3.4.4 strain at each temperature indicated that the majority displayed different survival kinetics from the other strains at 4 °C and 20 °C.
... AIVs are negative-strand RNA viruses of the Orthomyxoviridae family that contain two surface glycoproteins i.e. hemagglutinin (HA) and neuraminidase (NA) [13]. Based on these surface glycoproteins, AIVs are serologically classified into 9 NA (N1-N9) and 18 HA (H1-H18) subtypes [14,15]. AIVs are classified into two pathotypes on the basis of pathogenicity characteristics in chicken and molecular attributes of HA cleavage site (HACS) i.e. highly pathogenic avian influenza virus (HPAIV) and the low pathogenic avian influenza virus (LPAIV) [16]. ...
Background
In this study, we investigated the prevalence of respiratory viruses in four Hybrid Converter Turkey (Meleagris gallopavo) farms in Egypt. The infected birds displayed severe respiratory signs, accompanied by high mortality rates, suggesting viral infections. Five representative samples from each farm were pooled and tested for H5 & H9 subtypes of avian influenza viruses (AIVs), Avian Orthoavulavirus-1 (AOAV-1), and turkey rhinotracheitis (TRT) using real-time RT-PCR and conventional RT-PCR. Representative tissue samples from positive cases were subjected to histopathology and immunohistochemistry (IHC).
Results
The PCR techniques confirmed the presence of AOAV-1 and H5 AIV genes, while none of the tested samples were positive for H9 or TRT. Microscopic examination of tissue samples revealed congestion and hemorrhage in the lungs, liver, and intestines with leukocytic infiltration. IHC revealed viral antigens in the lungs, liver, and intestines. Phylogenetic analysis revealed that H5 HA belonged to 2.3.4.4b H5 sublineage and AOAV-1 belonged to VII 1.1 genotype.
Conclusions
The study highlights the need for proper monitoring of hybrid converter breeds for viral diseases, and the importance of vaccination programs to prevent unnecessary losses. To our knowledge, this is the first study that reports the isolation of AOAV-1 and H5Nx viruses from Hybrid Converter Turkeys in Egypt.
... Avian influenza viruses can be excreted from the feces and respiratory secretions of infected birds and are transmitted between birds by the fecal-oral route and the respiratory route [10][11][12]. Compared with H5N1 HPAI, H5N8 HPAI was more excreted in wild ducks and could reach the level of direct contact transmission [13]. ...
H5N8 HPAI is a highly infectious avian disease that now poses a serious threat and potential risk to poultry farming, wild birds, and public health. In this study, to investigate the seasonality and transmission directionality of global H5N8 HPAI, the spatial and temporal analysis of H5N8 HPAI was conducted using time series decomposition and directional distribution analysis. An ecological niche model was developed for H5N8 HPAI in poultry to identify areas at high risk of H5N8 HPAI in poultry and associated risk factors. The results indicated that three global pandemics of H5N8 HPAI emerged from 2014 to 2022, all showing a southeast–northwest distribution direction. H5N8 HPAI occurred more frequently in winter and less frequently in summer. The southwestern border region and the southeastern region of North America, the southern region of South America, most of Europe, the southern border region and the northern border region of Africa, and the southwestern region and the southeastern region of Asia provide the suitable environment for the occurrence of H5N8 HPAI in poultry. Chicken density, duck density, population density, bio1 (annual mean temperature), and land cover were considered important variables for the occurrence of H5N8 HPAI in poultry. This study can help optimize the use of resources and provide new information for policymakers to carry out prevention and control efforts.
... The molecular properties of HA and NA proteins determine FLUAV classification into subtypes [6]. A total of 19 HA (H1-H19) and 11 NA (N1-N11) have been recognized, with H17N10 and H18N11 "flu-like" subtypes exclusively isolated in bats ( Figure 1) [7][8][9][10][11]. Wild waterfowl (Anseriformes, Charadriiformes) are considered the natural reservoir of 17 of 19 HA (H1-16 and H19) and 9 of 11 NA (N1-9) AIV subtypes, and they carry AIVs mostly subclinically [12]. ...
Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, leading to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry and agriculture. Since their first isolation in 2013-2014, the Asian-origin H5 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and reassortment of internal gene segments. In just a few years, it supplanted other AIV clades, and now it is widespread in the wild migratory waterfowl, spreading to Asia, Europe, Africa, and the Americas. Wild waterfowl, the natural reservoir of LPAIVs and generally more resistant to the disease, also manifested high morbidity and mortality with HPAIV clade 2.3.4.4b. This clade also caused overt clinical signs and mass mortality in a variety of avian and mammalian species never reported before, such as raptors, seabirds, sealions, foxes, and others. Most notably, the recent outbreaks in dairy cattle were associated with the emergence of a few critical mutations related to mammalian adaptation, raising concerns about the possibility of jumping species and acquisition of sustained human-to-human transmission. The main clinical signs and anatomopathological findings associated with clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.
... Avian influenza viruses (AIVs) demonstrate a broad host tropism, infecting a diverse array of host species, encompassing both domesticated avian species and various wild avifauna. Certain highly pathogenic avian influenza viruses (HPAIVs) have been documented to induce severe and often fatal illness in humans [47]. Achieving a precise laboratory diagnosis of AIV infections demands meticulous adherence to time-consuming and logistically intricate precautionary measures during specimen or virus shipment, in order to mitigate potential biohazard exposure risking its effectiveness. ...
Simple Summary
The instability of viral RNA, which is susceptible to ubiquitous RNases, poses a significant challenge for its transport and detection in diagnosis. To address this challenge, this study aimed to evaluate the stability and detection limits of various RNA viruses, including the avian influenza virus, Newcastle disease virus, and African horse sickness virus, on Flinders Technology Associates cards. This investigation provides empirical evidence supporting the efficacy of Flinders Technology Associates cards for sample collection and subsequent viral RNA recovery, highlighting their suitability for use in molecular diagnostics. Consequently, based on the demonstrated effectiveness, stability, and safety implications observed in this study, Flinders Technology Associates cards are recommended for virus storage and transport, thus facilitating the molecular detection and identification of RNA viral pathogens.
Abstract
The Flinders Technology Associates (FTA) card, a cotton-based cellulose membrane impregnated with a chaotropic agent, effectively inactivates infectious microorganisms, lyses cellular material, and fixes nucleic acid. The aim of this study is to assess the stability and detection limit of various RNA viruses, especially the avian influenza virus (AIV), Newcastle disease virus (NDV), and African horse sickness virus (AHSV), on the FTA card, which could significantly impact virus storage and transport practices. To achieve this, each virus dilution was inoculated onto an FTA card and stored at room temperature in plastic bags for durations ranging from 1 week to 6 months. Following storage, the target genome was detected using conventional reverse transcription polymerase chain reaction. The present study demonstrated that the detection limit of AIV ranged from 1.17 to 6.17 EID50 values over durations ranging from 1 week to 5 months, while for NDV, it ranged from 2.83 to 5.83 ELD50 over the same duration. Additionally, the detection limit of AHSV was determined as 4.01 PFU for both 1 and 2 weeks, respectively. Based on the demonstrated effectiveness, stability, and safety implications observed in the study, FTA cards are recommended for virus storage and transport, thus facilitating the molecular detection and identification of RNA viral pathogens.
... Penyakit Avian Influenza belum bisa diberantas di Indonesia dan penyakit ini masih endemis di Bali (Pratiwi et al., 2020). Sejak tahun 2002, virus AI menyebar hampir ke seluruh bagian dunia (Alexander, 2007) termasuk Indonesia (Kandun et al., 2006). Di Indonesia, penyakit ini di klasifikasikan sebagai salah satu penyakit infeksius yang perlu di prioritaskan dan di kontrol (Santhia et al., 2009). ...
Avian Influenza (AI) is still endemic in Bali. This disease is very dangerous and deadly, is zoonotic in birds and humans and causes high economic losses. AI disease in poultry is caused by the Influenza virus type A. The aim of the examination is to identify the agent that caused the death of the chicken in the case to determine a definite diagnosis. The case chicken sample was a 29 day old broiler chicken from a farm in Jatiluwih Village, Tabanan Regency, Bali. Clinical symptoms of chickens include: weak chickens, shaking, shortness of breath, no appetite for eating or drinking, dull feathers, pale bluish combs, runny discharge from the beak, and white-brown watery feces. Chicken death occurred 2 days after clinical symptoms appeared. After the chicken dies, a necropsy is carried out and the samples are examined in the histopathology, virology, bacteriology and parasitology laboratories to determine the agent that caused the death. Histopathological examination showed that all organs had lesions. The results of the HA/HI test showed that the chicken was a positive case of being infected with the Avian Influenza virus. Bacterial infection testing in the media test, selective test, primary test, secondary test and confectionery test identified the presence of Staphylococcus sp bacteria. in the liver and lungs. The results of fecal examination during parasite examination using native and concentration methods did not reveal any worm eggs or protozoa. It was concluded that the case chicken was infected with Avian Influenza with secondary bacterial infection, namely Staphylococcus sp. It is recommended that breeders improve biosecurity and carry out routine and appropriate vaccinations to prevent Avian Influenza disease.
... Migratory birds became vectors, facilitating the spread of the virus across diverse regions in Europe, Asia, and Africa [6]. Wild birds, often asymptomatic carriers of various AIV subtypes, play a critical role in the global transmission of avian influenza to domesticated birds [7]. The Mediterranean and East African migration flyways were identified as potential routes for the introduction of the HPAI H5N8 clade 2.3.4.4b into Egyptian poultry [8]. ...
... Global public health is greatly threated by emerging infectious diseases [1][2][3]. Since the 21st century, public health emergencies caused by major viral infectious diseases such as SARS (2003), avian influenza (2006), influenza A (2009), Ebola (2014), Zika (2015), and SARS-COV-2 (2019) have occurred more frequently [3][4][5][6][7][8]. Infectious disease outbreaks pose a major threat to the health of people or animals in close contact with each other, which also threatens worldwide economic development. ...
... The influenza virus is an RNA virus part of the Orthomyxoviridae family with seven genera, namely Influenzavirus A, Influenzavirus B, Influenzavirus C, Influenzavirus D, Thogotovirus, and Isavirus and Quarajavirus [24,25]; moreover, Influenzavirus A has been identified in a wide range of hosts with the highest genetic variability and is the only one capable of infecting birds [26,27]. Moreover, due to the segmented nature of the viral genome, new strains can emerge through genetic reassortment and antigenic drift, further increasing the difficulty in its control and prevention [28]. ...
Citation: Simancas-Racines, A.; Cadena-Ullauri, S.; Guevara-Ramírez, P.; Zambrano, A.K.; Simancas-Racines, D. Avian Influenza: Strategies to Manage an Outbreak. Pathogens 2023, 12, 610. Abstract: Avian influenza (AI) is a contagious disease among the poultry population with high avian mortality, which generates significant economic losses and elevated costs for disease control and outbreak eradication. AI is caused by an RNA virus part of the Orthomyxoviridae family; however, only Influenzavirus A is capable of infecting birds. AI pathogenicity is based on the lethality, signs, and molecular characteristics of the virus. Low pathogenic avian influenza (LPAI) virus has a low mortality rate and ability to infect, whereas the highly pathogenic avian influenza (HPAI) virus can cross respiratory and intestinal barriers, diffuse to the blood, damage all tissues of the bird, and has a high mortality rate. Nowadays, avian influenza is a global public health concern due to its zoonotic potential. Wild waterfowl is the natural reservoir of AI viruses, and the oral-fecal path is the main transmission route between birds. Similarly, transmission to other species generally occurs after virus circulation in densely populated infected avian species, indicating that AI viruses can adapt to promote the spread. Moreover, HPAI is a notifiable animal disease; therefore, all countries must report infections to the health authorities. Regarding laboratory diagnoses, the presence of influenza virus type A can be identified by agar gel immunodiffusion (AGID), enzyme immunoassay (EIA), immunofluorescence assays, and enzyme-linked immunoadsorption assay (ELISAs). Furthermore, reverse transcription polymerase chain reaction is used for viral RNA detection and is considered the gold standard for the management of suspect and confirmed cases of AI. If there is suspicion of a case, epidemiological surveillance protocols must be initiated until a definitive diagnosis is obtained. Moreover, if there is a confirmed case, containment actions should be prompt and strict precautions must be taken when handling infected poultry cases or infected materials. The containment measures for confirmed cases include the sanitary slaughter of infected poultry using methods such as environment saturation with CO 2 , carbon dioxide foam, and cervical dislocation. For disposal, burial, and incineration, protocols should be followed. Lastly, disinfection of affected poultry farms must be carried out. The present review aims to provide an overview of the avian influenza virus, strategies for its management, the challenges an outbreak can generate, and recommendations for informed decision making.
... Influenza A viruses are classified according to the antigenic properties of the surface glycoproteins HA and NA into 16 HA and 9 NA subtypes identified in poultry and wild birds (Wang et al., 2022). All avian influenza virus subtypes have been reported in wild birds, the natural reservoir, which usually shows asymptomatic infections, with few reported cases suffering from clinical signs (Alexander, 2007). ...
This study was conducted to investigate the epidemiological situation of avian influenza viruses (AIV) and the
molecular identification of the different AIV subtypes circulating among chickens and duck farms in South Egypt. A total of 143 samples were collected from chicken and duck farms in Qena (n = 105) and Luxor (n=38) governorates during 2020. The organs and swabs were collected from diseased chickens and healthy ducks. The viruses were isolated in embryonated chicken eggs (ECEs) and their propagation was confirmed by hemagglutination test (AHT) and molecular detection of matrix gene by reverse transcription polymerase chain reaction (RT-PCR). AIV subtypes were identified by RT-PCR and specific primers. Phylogenetic analysis of sequenced partial H5, N2, and N8 genes was performed. The results revealed that 15 AIVs were subtyped to 2 H5N2, 2
H5N8, 8 H5Nx, and 2 H9N2. While an isolate could not be subtyped by used primers. The H5-based evolutionary
tree of 4 isolates revealed their categorization with the 2.3.4.4b clade with close relation to H5N8 isolates from
Egypt in 2021 and Kazakhstan in 2020. In conclusion, the occurrence of H5 and H9 viruses pays attention to a public health concern. Also, non-identified HxNx reveals a new AIV HA and NA subtype may be present among chickens.
The avian influenza is a serious infection caused by influenza virus that is native to birds. Avian influenza remains a global challenge due to high transmission and mortality rates. The highly pathogenic strain of H5N1 resulted in significant outbreaks and deaths globally since the late 1800s. The most recent outbreaks in wild birds, domestic birds, and cows with some genetic variations and mutations among H5N1 strains has raised major concerns about potential transmission and public health risks. Symptoms range from asymptomatic to mild flu‐like illness to severe illness that requires hospitalization. There are multiple vaccines in development for humans to protect against avian influenza, specifically the H5N1 virus. This includes a cell‐based vaccine approved by the FDA for people aged 6 months and older who are at higher risk of exposure to the H5N1 virus called Audenz. Chemoprophylaxis against avian influenza following a suspected exposure should be started as soon as possible or no later than 48 h, and it is recommended to be continued for 7 days. The majority of avian influenza viruses are susceptible to neuraminidase inhibitors and cap‐dependent endonuclease inhibitor. Neuraminidase inhibitors are the mainstay of the avian influenza treatment and includes oseltamivir, peramivir, and zanamivir. Baloxavir marboxil is a cap‐dependent endonuclease inhibitor. This clinical review aims to highlight the background, epidemiology, clinical presentation, complications and current treatment and prevention strategies for avian influenza H5N1.
Competent authorities of many countries, including Belgium, impose control measures (preventing wild bird access to feeders and water facilities, indoor confinement of captive birds, or fencing off outdoor ranges with nets) on professional and non-professional keepers of birds to prevent the spread of avian influenza (AI). Flemish laying hen farmers (FAR, n = 33) and private keepers of captive birds (PRI, n = 263) were surveyed about their opinion on and compliance with AI measures legally imposed during the most recent high-risk period before this survey in 2021. Participants answered questions on a 5-point Likert scale (1 = the worst, 3 = neutral, and 5 = the best). FAR indicated better compliance with the AI measures than PRI, except for net confinement. FAR indicated that they and other poultry farmers complied better with AI measures than PRI. Additionally, PRI indicated that they better complied than other PRI keepers. FAR regarded the AI measures as more effective than PRI. To prevent the spread of AI more effectively, national authorities could focus on information campaigns explaining to private bird keepers the need for the various control measures that they impose. If these campaigns fail, local authorities may need stricter enforcement or alternative ways to increase compliance.
The consumption of wild game meat, rooted in cultural traditions and increasingly favored as a natural food source, presents both nutritional benefits and toxicological challenges. While wild game offers a rich source of protein and essential nutrients, it also carries unique risks associated with environmental contaminants, naturally occurring toxins, and zoonotic diseases. This review provides a comprehensive analysis of these toxicological hazards, drawing from a wide range of scientific literature. It examines the origins of toxins in wild game, including heavy metals, pesticides, and other environmental pollutants, as well as the risks posed by animals' natural diets and traditional hunting methods. Additionally, the review addresses the public health implications of consuming contaminated wild game and offers strategies for mitigating these risks. By exploring the complex interplay between wild game consumption and toxicology, this review aims to inform both consumers and public health professionals, emphasizing the importance of safe practices in the handling and preparation of wild game meat to minimize potential health hazards.
Objective: Avian influenza virus (AIV) infections first affect the respiratory tract of chickens. The epithelial cells activate the host immune system, which leads to the induction of immune-related genes and the production of antiviral molecules against external environmental pathogens. In this study, we used chicken tracheal epithelial cells (TECs) in vitro model to investigate the immune response of the chicken respiratory tract against avian respiratory virus infections.Methods: Eighteen-day-old embryonic chicken eggs were used to culture the primary chicken TECs. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry (ICC) analysis of epithelial cell-specific gene makers were performed to confirm the characteristics, morphology, and growth pattern of primary cultured chicken TECs. Moreover, to investigate the cellular immune response to AIV infection or polyinosinic-polycytidylic acid (poly [I:C]) treatment, the TECs were infected with the H5N1 virus or poly (I:C). Then, immune responses were validated by RT-qPCR and western blotting.Results: The TECs exhibited polygonal morphology and formed colony-type cell clusters. The RT-qPCR results showed that H5N1 infection induced a significant expression of antiviral genes in TECs. We found that TECs treated with poly (I:C) and exposed to AIV infection-mediated activation of signaling pathways, leading to the production of antiviral molecules (e.g., pro-inflammatory cytokines and chemokines), were damaged due to the loss of junction proteins. We observed the activation of the nuclear factor kappa B and mitogen-activated protein kinase (MAPK) pathways, which are involved in inflammatory response by modulating the release of pro-inflammatory cytokines and chemokines in TECs treated with poly (I:C) and pathway inhibitors. Furthermore, our findings indicated that poly (I:C) treatment compromises the epithelial cell barrier by affecting junction proteins in the cell membrane.Conclusion: Our study highlights the utility of in vitro TEC models for unraveling the mechanisms of viral infection and understanding host immune responses in the chicken respiratory tract.
Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, lead-ing to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry. Since their first isolation in 2013, the Asian-origin H5N1 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and re-assortment of internal gene segments and have spread to Asia, Europe, Africa, and America, caus-ing outbreaks in all the poultry categories. Novel epidemiological and pathobiological character-istics, distinct from other clades, are specific of clade 2.3.4.4b viruses. Wild waterfowl, the natu-ral reservoir of AIVs, are frequently found infected with clade 2.3.4.4b viruses, which can also cause high morbidity and mortality in these birds. The sustained clade 2.3.4.4b virus circulation in waterfowl has also led to virus infection in other wild bird species, with implications for the conservation of endangered species. Furthermore, clade 2.3.4.4b viruses have been isolated in var-ious wild and domestic mammals worldwide, and critical mutations related to virus adaptation to mammalian species have been identified, raising concerns about virus spillover to humans. The main clinical signs, and anatomopathological findings associated to clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.
Unidentified diseases are becoming more prevalent among humans due to various
climatic factors, and some of these diseases originate in animals before spreading to
humans. One virus that has been of particular concern is the avian influenza virus,
which primarily infects bird and can subsequently transmit to humans. This article
presents a mathematical model describing the spatio-temporal reaction-diffusion process involved in the transmission of avian flu in human population. The paper begins by studying the proposed model’s well-posedness and the calculated basic reproduction number, which provides valuable insights into the dynamics of virus transmission. The paper also provides stability analysis for the disease-free steady state of the model. All theoretical studies are validated using computational results.
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sustainable future for all.
Avian influenza viruses (AIVs) have posed a significant pandemic threat since their discovery. This review mainly focuses on the epidemiology, virology, pathogenesis, and treatments of avian influenza viruses. We delve into the global spread, past pandemics, clinical symptoms, severity, and immune response related to AIVs. The review also discusses various control measures, including antiviral drugs, vaccines, and potential future directions in influenza treatment and prevention. Lastly, by summarizing the insights from previous pandemic control, this review aims to direct effective strategies for managing future influenza pandemics.
High pathogenicity avian influenza (HPAI) H5N1 outbreaks pose a significant threat to the health of livestock, wildlife, and humans. Avian influenza viruses (AIVs) are enzootic in poultry in many countries, including Bangladesh, necessitating improved farm biosecurity measures. However, the comprehension of biosecurity and hygiene practices, as well as the infection of AIV in turkey farms, are poorly understood in Bangladesh. Therefore, we conducted this study to determine the prevalence of AIV subtypes and their association with biosecurity and hygiene practices in turkey farms. We collected oropharyngeal and cloacal swabs from individual turkeys from 197 farms across 9 districts in Bangladesh from March to August 2019. We tested the swab samples for the AIV matrix gene (M gene) followed by H5, H7, and H9 subtypes using real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). We found 24.68% (95% CI:21.54–28.04) of turkey samples were AIV positive, followed by 5.95% (95% CI: 4.33–7.97) for H5, 6.81% (95% CI: 5.06–8.93) for H9 subtype and no A/H7 was found. Using a generalized linear mixed model, we determined 10 significant risk factors associated with AIV circulation in turkey farms. We found that the absence of sick turkeys, the presence of footbaths, the absence of nearby poultry farms, concrete flooring, and the avoidance of mixing newly purchased turkeys with existing stock can substantially reduce the risk of AIV circulation in turkey farms (odds ratio ranging from 0.02 to 0.08). Furthermore, the absence of nearby live bird markets, limiting wild bird access, no visitor access, improved floor cleaning frequency, and equipment disinfection practices also had a substantial impact on lowering the AIV risk in the farms (odds ratio ranging from 0.10 to 0.13). The results of our study underscore the importance of implementing feasible and cost-effective biosecurity measures aimed at reducing AIV transmission in turkey farms. Particularly in resource-constrained environments such as Bangladesh, such findings might assist governmental entities in enhancing biosecurity protocols within their poultry sector, hence mitigating and potentially averting the transmission of AIV and spillover to humans.
Changes to migration routes and phenology create novel contact patterns among hosts and pathogens. These novel contact patterns can lead to pathogens spilling over between resident and migrant populations. Predicting the consequences of such pathogen spillover events requires understanding how pathogen evolution depends on host movement behaviour. Following spillover, pathogens may evolve changes in their transmission rate and virulence phenotypes because different strategies are favoured by resident and migrant host populations. There is conflict in current theoretical predictions about what those differences might be. Some theory predicts lower pathogen virulence and transmission rates in migrant populations because migrants have lower tolerance to infection. Other theoretical work predicts higher pathogen virulence and transmission rates in migrants because migrants have more contacts with susceptible hosts.
We aim to understand how differences in tolerance to infection and host pace of life act together to determine the direction of pathogen evolution following pathogen spillover from a resident to a migrant population.
We constructed a spatially implicit model in which we investigate how pathogen strategy changes following the addition of a migrant population. We investigate how differences in tolerance to infection and pace of life between residents and migrants determine the effect of spillover on pathogen evolution and host population size.
When the paces of life of the migrant and resident hosts are equal, larger costs of infection in the migrants lead to lower pathogen transmission rate and virulence following spillover. When the tolerance to infection in migrant and resident populations is equal, faster migrant paces of life lead to increased transmission rate and virulence following spillover. However, the opposite can also occur: when the migrant population has lower tolerance to infection, faster migrant paces of life can lead to decreases in transmission rate and virulence.
Predicting the outcomes of pathogen spillover requires accounting for both differences in tolerance to infection and pace of life between populations. It is also important to consider how movement patterns of populations affect host contact opportunities for pathogens. These results have implications for wildlife conservation, agriculture and human health.
Clade 2.3.4.4b highly pathogenic avian influenza A (HPAI) viruses have been detected in wild birds worldwide, causing recurrent outbreaks since 2016. During the winter of 2021–2022, we detected 1 H5N8 and 43 H5N1 clade 2.3.4.4b HPAI viruses from wild birds in South Korea. Phylogenetic analysis revealed that HA gene of H5N1 viruses was divided into two genetically distinct groups (N1.G1 and N1.G2). Bayesian phylodynamic analysis demonstrated that wild birds play a vital role in viral transmission and long-term maintenance. We identified five genotypes (N1.G1.1, N1.G2, N1.G2.1, N1.G2.2, and N1.G2.2.1) having distinct gene segment constellations most probably produced by reassortments with low-pathogenic avian influenza viruses. Our results suggest that clade 2.3.4.4b persists in wild birds for a long time, causing continuous outbreaks, compared with previous clades of H5 HPAI viruses. Our study emphasizes the need for enhancing control measures in response to the changing viral epidemiology.
Zwischen dem Virus der klassischen Geflügelpest und Vertretern des Α-Typs der Influenza bestehen sero-immunologische Beziehungen, die mit Hilfe der Komplementbindungs-Probe und des Kreuzimmunisierungs-Versuches festgestellt wurden, durch den Präzipitations-, Hämagglutinations-Hemmungs- und Neutralisations-Versuch aber nicht nachzuweisen waren.
Die serologische Untersuchung der Spaltprodukte des Influenza-FM/
Ebenso wie die Influenza-Viren ließ sich auch das Geflügelpest-Virus durch intranasale Impfung auf die Lunge der weißen Maus übertragen. Es wurde auf diese Weise bisher in 14 Passagen fortgeführt.
Die Viren der Influenza und klassischen Geflügelpest sind auf Grund der Übereinstimmungen, die sie in physikalisch-chemischer und sero-immunologischer Hinsicht zeigen, nunmehr endgültig in eine Gruppe einzuordnen.
The outbreak of highly pathogenic avian influenza of the H5N1 subtype in Asia, which has subsequently spread to Russia, the Middle East, Europe, and Africa, has put increased focus on the role of wild birds in the persistence of influenza viruses. The ecology, epidemiology, genetics, and evolution of pathogens cannot be fully understood without taking into account the ecology of their hosts. Here, we review our current knowledge on global patterns of influenza virus infections in wild birds, discuss these patterns in the context of host ecology and in particular birds' behavior, and identify some important gaps in our current knowledge.
From the end of March to the beginning of December 1999, an epidemic of low pathogenicity avian influenza (LPAI) affected the industrial poultry population of northern Italy. The virus responsible for the epidemic was subtyped as H7N1 with an intravenous pathogenicity index (IVPI) of 0.0, and a deduced amino acid sequence of the region coding for the cleavage site of the haemagglutinin molecule typical of low pathogenicity viruses. The circulation of the virus in a susceptible population for several months caused the emergence of a highly pathogenic virus with an IVPI of 3.0 and the presence of multiple basic amino acids in the deduced amino acid sequence for the cleavage site of the haemagglutinin molecule. Over 13 million birds were affected by the epidemic and, in the present paper, we report the results of the clinical, virological and histopathological investigations performed on affected chickens and turkeys. Clinical, gross and microscopic lesions caused by LPAI were more severe in turkeys than in chickens, while highly pathogenicity avian influenza (HPAI) caused similar mortality rates in both species. Current European legislation considers LPAI and HPAI as two completely distinct diseases, not requiring any compulsory eradication policy for LPAI but enforcing eradication for HPAI. In the Italian 1999 to 2000 epidemic, LPAI mutated to HPAI in a densely populated area, causing great economic losses. A reconsideration of the current European Union legislation on avian influenza, including LPAI of the H5 and H7 subtypes, could possibly be an aid to avoiding devastating epidemics for the poultry industry.
Influenza A viruses isolated from the cloaca of naturally infected feral ducks replicate in the lungs and in the cells lining the intestinal tract of feral and domestic ducks. Despite the low pH of the gizzard, the duck influenza viruses reach the intestines via the digestive tract and are found in high concentration in the feces. The viruses retain infectivity in fecal material for at least 30 days at 4° and for 7 days at 20°. The morphology of one strain of intestinal duck influenza virus (Hav7 Neg2) that had never been passed in embryonated eggs and was isolated from the feces was roughly spherical and fairly uniform in size and shape. However, another strain of duck influenza virus studied (Hav3 Nav6) was predominantly filamentous, suggesting that the morphology of influenza viruses in their natural hosts varies from strain to strain. After passage in the chick embryo each strain retained the morphological characteristics found in the feces. In contrast to duck influenza viruses, representative human influenza viruses of the HON1, H3N2, and Hswl Nl subtypes replicate only in the upper respiratory tract of ducks. The duck influenza viruses are more stable to low pH than human strains and retain infectivity for over 30 days in nonchlorinated river water at 0° and for 4 days at 22°. The susceptibility of ducks to infection with human and avian strains of influenza virus and the possibility of transmission to animal species through the water supply suggests that ducks may be important in the ecology of influenza viruses. The possibility of “intestinal influenza” virus vaccines is considered.
Many viruses have membrane glycoproteins that are activated at cleavage sites containing multiple arginine and lysine residues by cellular proteases so far not identified. The proteases responsible for cleavage of the hemagglutinin of fowl plague virus, a prototype of these glycoproteins, has now been isolated from Madin-Darby bovine kidney cells. The enzyme has a mol. wt of 85,000, a pH optimum ranging from 6.5 to 7.5, is calcium dependent and recognizes the consensus sequence R-X-K/R-R at the cleavage site of the hemagglutinin. Using a specific antiserum it has been identified as furin, a subtilisin-like eukaryotic protease. The fowl plague virus hemagglutinin was also cleaved after coexpression with human furin from cDNA by vaccinia virus vectors. Peptidyl chloroalkylketones containing the R-X-K/R-R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity.
The amino acid sequences at the haemagglutinin cleavage sites of 9 avian influenza A viruses of H5 subtype (5 high and 4 low pathogenicity for chickens) and 21 of H7 subtype (13 high and 8 low pathogenicity for chickens) were determined by direct RNA sequencing, PCR amplification sequencing or both. None of the viruses of low pathogenicity had multiple basic amino acids at the cleavage site. All highly pathogenic viruses had an insert of basic amino acids at the cleavage site, except A/chicken/Scotland/59 (H5N1) for which the multiple basic amino acids appeared as substitutions and not insertions. All highly pathogenic viruses examined conformed to the amino acid motif of R-X-R/K-R at the cleavage site which is considered to be essential for high pathogenicity in chickens, with the notable exception of highly pathogenic virus A/turkey/England/50-92/91 (H5N1) which had the sequence R-K-R-K-T-R adjacent to the cleavage site.
A 945 nucleotide region (bases 76-1020) of the HA1 part of the HA gene was obtained for 31 influenza viruses of H7 subtype isolated primarily from Europe, Asia and Australia over the last 20 years. These were analysed phylogenetically and compared with sequences of the same region from 23 H7 subtype viruses available in Genbank. The overall results showed two geographically distinct lineages of North American and Eurasian viruses with major sublineages of Australian, historical European and equine viruses. Genetically related sublineages and clades within these major groups appeared to reflect geographical and temporal parameters rather than being defined by host avian species. Viruses of high and low virulence shared the same phylogenetic branches, supporting the theory that virulent viruses are not maintained as a separate entity in waterfowl.
A 380 nucleotide region (bases 613 to 992) of the HA1 part of the haemagglutinin (H) gene was obtained for 35 influenza viruses of H9 subtype isolated from around the world over the past 33 years. These were analyzed phylogenetically and compared with sequences from 19 H9 subtype viruses available in the Genbank database. These viruses do not show such clear geographical lineages as other subtypes (i.e. H5 or H7) and there is a high degree of variation at the cleavage site of the haemagglutinin. Genetically distinct lineages of H9 viruses have circulated contemporaneously in different locations. Thus, it is likely that the numerous infections of poultry and other birds with H9 subtype influenza viruses during the 1990s originate from separate introductions from feral birds. The observed heterogeneity of these viruses may reflect the gene pool for H9 viruses, which is maintained in shorebirds and gulls (Charadriiformes).
A worrying development could help to spread this dangerous virus beyond its stronghold in southeast Asia. The highly pathogenic H5N1 influenza virus has become endemic in poultry in southeast Asia since 2003 and constitutes a major pan-demic threat to humans 1 . Here we describe cases of disease caused by H5N1 and trans-mission of the virus among migratory geese populations in western China. This outbreak may help to spread the virus over and beyond the Himalayas and has important implications for developing control strategies. H5N1 virus has occasionally been isolated from dead wild birds, usually within the flight range of infected poultry farms 2,3 . In the absence of evidence that the virus is transmit-ted within wild bird populations or that migra-tory birds can carry the virus, it was possible that these birds were dead-end hosts of virus acquired from poultry. On 30 April 2005, however, an outbreak was detected in bar-headed geese (Anser indicus) at Qinghai Lake in western China (see supplementary infor-mation), which is a protected nature reserve with no poultry farms in the vicinity. Initially, sick bar-headed geese were recorded on a single islet that contained about 3,000 bar-headed geese as well as some brown-headed gulls (Larus brunnicephalus), great black-headed gulls (Larus ichthyaetus) and great cormorants (Phalacrocorax carbo). Clin-ical findings included paralysis, unusual head tilt, staggering and neck thrill — all are known features of H5N1 disease in waterfowl. By 4 May, bird mortality was more than 100 a day; by 20 May, the outbreak had spread to other islets, with some 1,500 birds dead. Overall, 90% of the dead birds were bar-headed geese, with the remainder being brown-headed gulls and great black-headed gulls. We isolated 28 H5N1 viruses from 92 cloacal, tracheal and faecal swabs from all three species, and a further 5 viruses from tissue samples from bar-headed geese. (For details of methods, see supplementary information.) Sequence comparison revealed that the H5N1 viruses were almost identical across all gene segments. The haemagglutinin gene retains the motif of basic amino acids (QGER-RRKKR) in the connecting peptide that charac-terizes highly pathogenic avian flu. All Qinghai isolates had a Lys 627 mutation in the PB2 gene, which has been associated with increased viru-lence in mice 4 . Phylogenetic analysis of these isolates and eight other H5N1 viruses, isolated from poultry markets in Fujian, Guangdong, Hunan and Yunnan provinces during 2005, indicated that the haemagglutinin (Fig. 1a), neuraminidase and nucleoprotein (data not shown) genes of the Qinghai viruses were closely related to the H5N1 virus A/Chicken/ Shantou/4231/2003 (genotype V). However, the other five internal genes, rep-resented by the matrix-protein gene, were closely related to H5N1 viruses isolated from domestic poultry in southern China during 2005, represented by the virus A/Chicken/ Shantou/810/2005 (genotype Z) (Fig. 1b). These viruses are therefore characterized as H5N1 genotype Z, but are clearly distinguish-able from those that have caused human infec-tion in Thailand and Vietnam (Fig. 1a, b) 5 . This indicates that the virus causing the outbreak at Qinghai Lake was a single introduction, most probably from poultry in southern China. Qinghai Lake is an important aggregation and breeding site for bar-headed geese that are distributed over central Asia 6 . From Septem-ber, they migrate southwards to Myanmar and over the Himalayas to India, returning to Qinghai around April 6 . Our findings indicate that H5N1 viruses are now being transmitted between migratory birds at the lake. Although the outbreak could burn itself out, the large migratory bird population at Qinghai Lake makes this unlikely. The viruses might also move to other migratory species that could act as carriers, remaining highly pathogenic for domestic chickens and possibly humans. Like its precursor, A/Goose/Guangdong/ 1/96, the current H5N1 virus could become established in bar-headed geese. There is a danger that it might be carried along the birds' winter migration routes to densely populated areas in the south Asian subcontinent, a region that seems free of this virus, and spread along migratory flyways linked to Europe. This would vastly expand the geographical distrib-ution of H5N1. Increased surveillance of poul-try is called for because previous experience has shown that control measures become almost impossible once the virus is entrenched in poultry populations.
In transmission experiments, the influenza A virus isolate turkey/ Ontario 7732/66 caused an acute disease in chickens and turkeys, but was apathogenic to ducks, geese and pigeons. After an incubation period from two to eight days, turkeys and chickens became rapidly depressed and died usually within the following four days. Other clinical signs were variable for the two gallinaceous species, such as exudative head swellings and gangrenous comb lesions in chickens, and diarrhea in turkeys. Infection by even minimal virus doses was fatal in turkeys, whereas chickens sometimes recovered from the disease or remained unaffected by the infection. Serial passage of the virus in chicken embryos accentuated this difference in species susceptibility still more. The infection spread easily by close contact among turkeys, but less among chickens.
The signs and course of the disease by virus 7732 are compared to those described for classical fowl plague, and it is concluded that these two avian influenza virus infections cannot be differentiated by clinical criteria.
From 1997 to 2001, Italy has been affected by two epidemics of high-pathogenicity avian influenza. The first epidemic was caused by a virus of the H5N2 subtype and was limited to eight premises in backyard and semi-intensive flocks. The prompt identification of the disease was followed by the implementation of European Union (EU) directive 92/40/EEC and resulted in the eradication of infection without serious consequences to the poultry industry. The 1999-00 epidemic was caused by a virus of the H7N1 subtype that originated from the mutation of a low pathogenic virus and resulted instead in a devastating epidemic that affected industrially reared poultry, culminating in the infection of 413 flocks. The description of the epidemics and the result of the control policies are reported.
The aetiological agent of an epizootic among Common Terns ( Sterna hirundo ) in South Africa in 1961 was isolated from several sick birds and named Tern virus. It was classified on the basis of antigenic and morphological properties as a strain of avian influenza virus, Myxovirus influenzae A/Tern/South Africa/1961. The strain-specific antigen of Tern virus was unrelated to all known influenza strains with the single exception of Chicken/Scotland/1959 virus and the two viruses may be regarded as variants of the same strain. This relationship raised the interesting epidemiological possibility of the spread of infection between sea-birds and domestic poultry because the Common Tern migrates between Europe and South Africa.
The pathogenicity of three Australian fowl plague viruses, FPV-1, FPV-2, FPV-3, isolated during a natural outbreak of the disease varied for chickens, turkeys and ducks. FPV-1 and FPV-2 were pathogenic for chickens and turkeys, but not for ducks. However, these viruses were not highly pathogenic as they failed to cause illness or death in all birds that became infected. FPV-3 was non-pathogenic for the three species tested.The viruses spread from infected to in-contact birds, and more readily to ducks than to chickens or turkeys. All chickens and turkeys infected with the fowl plague viruses developed specific serum haemagglutination-inhibiting antibody which persisted for up to 85 days after infection. The titre of this antibody wan ed in six of 16 ducks over an 85-day period and two ducks failed to produce detectable specific HaI antibody despite being infected with the virus.
Groups of 10 two-week-old chicks, turkey poults and ducklings were each infected by the intranasal route with one of four avian influenza viruses: a/fowl/Germany/34 (Hav 1N))--Rostock, A/FPV/Dutch/27 (Hav 1 Neq 1)--Dutch, A/fowl/Victoria/75 (Hav 1 Neq 1)--Australian, and A/parrot/Ulster/73 (Hav 1 N1)--Ulster. Eight hours after infection 10 birds of the same age and species were placed in contact with each group and allowed to mix. The clinical signs of disease and onset of sickness and death were recorded. Ulster virus was completely avirulent for all birds. Rostock, Dutch and Australian viruses were virulent for fowls and turkeys causing death in all birds with the exception of 3/10 in contact fowls from the Rostock virus group and 2/10 in contact fowls from the Australian virus group. Only Rostock virus caused sicked sickness or death in ducks, 9/10 intranasally infected and 6/7 in contact birds showed clinical signs and 2/10 intranasally infected and 3/7 in contact ducks died. Intranasal and in contact pathogenicity indices were calculated for each virus in each bird species and indicated quantitatively the differences in virulence of the four virus strains. Virus isolation and immune response studies indicated that surviving in contact fowls in the Rostock virus group had never been infected but that surviving Australian virus in contact fowls had recovered from infection. Infection was not established in Ulster virus in contact fowls and Australian virus intranasally infected and in contact ducks. The birds in all other groups showed positive virus isolations and a high incidence of positive immune response. The last virus isolation was made at 22 days after intranasal infection of ducks with Ulster virus.
Clinical signs, death, virus excretion and immune response were measured in 2-week-old chickens, turkeys, quail and ducks infected by intramuscular, intranasal and contact routes with eight influenza viruses of H5 subtype. Six of the viruses: A/chicken/Scotland/59 (H5N1), ck/Scot; A/tern/South Africa/61 (H5N3), tern/SA; A/turkey/Ontario/ 7732/66 (H5N9); ty/Ont; A/chicken/Pennsylvania/1370/83 (H5N2); Pa/1370; A/turkey/Ireland/83 (H5N8); ty/Ireland, and A/duck/Ireland/ 113/84 (HSN8); dk/Ireland, were highly pathogenic for chickens and turkeys. Two viruses, A/chicken/Pennsylvania/1/83 (H5N2), Pa/1 and A/turkey/Italy/ZA/80 (H5N2), ty/Italy, were of low pathogenicity. Ck/Scot was more pathogenic for chickens than turkeys while ty/Ont was more pathogenic for turkeys than chickens. Other viruses showed little difference in their pathogenicity for these two hosts. No clinical signs or deaths were seen in any of the infected ducks. Only two viruses, dk/Ireland and ty/Ireland, produced consistent serological responses in ducks, although intramuscular infection with tern/SA and ty/Italy resulted in some ducks with positive HI titres. These four were the only viruses reisolated from ducks. Quail showed some resistance to viruses which were highly pathogenic for chickens and turkeys, most notably to ck/Scot and ty/Ont and to a lesser extent tern/SA and Pa/1370. Transmission of virus from intranasally infected birds to birds placed in contact varied considerably with both host and infecting virus and the various combinations of these.
Differences were demonstrated in the transmissibility of two strains of avian influenza virus among chickens. One strain, A/duck/Victoria/76 (H7N6) spread quickly and infected all incontact chickens, whereas A/chicken/Victoria/75 (H7N6) spread slowly and failed to infect all incontact chickens. These strains were isolated in the same locality at about the same time in a region where the viruses, and the disease fowl plague, had not been previously recognised. Resume Des différences ont été mises en évidence dans la transmissibilité de deux souches d'influenza aviaire chez le poulet. Une souche A/duck/Victoria/76 (H7 N6) a disséminé rapidement et infecté tous les poulets mis en contact alors que la souche A/chicken/Victoria/75 (H7 N6) a disséminé lentement et n'a pas infecté tous les poulets mis en contact. Ces souches ont été isolées dans la même localité a peu près au même moment, dans une région o[ugrave] les virus de la peste aviaire et la maladie n'avaient pas été observés auparavant. Zusammenfassung Es wurde eine sehr unterschiedliche Übertragbarkeit von zwei aviären Influenza Virusstämmen zwischen Hühnern aufgezeigt. Ein Virusstamm A/Ente/Victoria/76 (H7 N6) breitete sich schnell aus und infizierte alle Kontakthühner, während sich A/Huhn/ Victoria/75 (H7 N6) langsam ausbreitete und nicht alle Kontakttiere infizierte. Die Stämme waren am selben Ort, um etwa die gleiche Zeit, in einem Gebiet isoliert worden, wo diese Viren und die Hühnerpest vorher nicht festgestellt worden waren.
The isolation of influenza A viruses from unconcentrated lake water and from fecal samples on the shore of these lakes is reported for the first time. Influenza A viruses, representative of most of the major antigenic subtypes, co-circulate in ducks on the lakes.
Influenza viruses, like other viruses, must exhibit a genome constellation, which permits optimal virus reproduction in a given host. Besides this prerequisite the influenza virus haemagglutinin glycoprotein (HA) has been shown to be an essential determinant for pathogenicity. HA, which is synthesized as a precursor molecule, is activated by posttranslational cleavage by host proteases to obtain its full biological properties. Proteolytic activation is therefore indispensable for effective virus spread in the infected host and thus for pathogenicity. HA of the highly pathogenic avian influenza viruses inducing a systemic infection in birds is cleaved in a broad range of different host cells. On the other hand, HA of all mammalian viruses and the nonpathogenic avian strains, which cause local infection, exhibit a restricted cleavability. The prime determinant for these differences has been found to be the structure of the cleavage site. This concept was corroborated on virus mutants adapted in vitro to a new host.
The hemagglutinin of influenza virus A/FPV/Rostock/34 (H7) was altered at its multibasic cleavage site by site-directed mutagenesis and assayed for proteolytic activation after expression in CV-1 cells. The results indicated that the cellular protease responsible for activation recognizes the tetrapeptide motif R-X-K/R-R that must be presented in the correct sequence position. Studies on plaque variants of influenza virus A/fowl/Victoria/75 (H7N7) showed that alteration of the consensus sequence resulted in a loss of pathogenicity for chickens.
Persistence of five avian influenza viruses (AIVs) derived from four waterfowl species in Louisiana and representing five hemagglutinin and neuraminidase subtypes was determined in distilled water at 17 C and 28 C. Infectivity was determined over 60 days by microtiter endpoint titration. One AIV was tested over 91 days at 4 C. Linear regression models for these viruses predicted that an initial concentration of 1 x 10(6) TCID50/ml water could remain infective for up to 207 days at 17 C and up to 102 days at 28 C. Significant differences in slopes for AIV persistence models were detected between treatment temperatures and among viruses. Results suggest that these viruses are adapted to transmission on waterfowl wintering habitats. Results also suggest a potential risk associated with waterfowl and domestic poultry sharing a common water source.
Influenza virus A/seal/Mass/1/80 (H7N7) was adapted to grow in MDCK cells and chicken embryo cells (CEC) in the absence of exogenous protease. The biological properties of the virus variants obtained coincided with intracellular activation of the hemagglutinin (HA) by posttranslational proteolytic cleavage and depended on the cell type used for adaptation. MDCK cell-adapted variants contained point mutations in regions of the HA more distant from the cleavage site. It is proposed that these mutations are probably responsible, through an unknown mechanism, for enhanced cleavability of HA in MDCK cells. Such virus variants were apathogenic in chickens. CEC-adapted variants, on the other hand, contained an insertion of basic amino acids at the HA cleavage site, in addition to scattered point mutations. The insertions converted the cleavage sites in the variant virus HAs so that they came to resemble the cleavage site found in highly pathogenic avian influenza viruses. CEC variants with such cleavage site modifications were highly pathogenic for chickens. The lethal outcome of the infection in chickens demonstrated for the first time that an influenza virus derived from a mammalian species can be modified during adaptation to a new cell type to such an extent that the resulting virus variant becomes pathogenic for an avian species.
Isolation of avian influenza virus (AIV) has been reported from 12 orders and 88 species of free-living birds. Most isolations are reported from species in the orders Anseriformes and Charadriiformes and it is recognized that species in Anseriformes represent important reservoirs of AIV. Morbidity and mortality among free-living birds attributable to AIV infection are rare, but differences in prevalence of AIV occur within and between avian species. Seasonal variation has been reported from free-living and sentinel ducks with peak AIV infection occurring in late summer and early fall. Prevalence of AIV is age-related, with highest isolation rates reported from juvenile birds. Differences in susceptibility to AIV infection among species have been demonstrated under experimental conditions. The dynamics and epidemiology of species-related variation in populations of free-living birds require further study.
Evidence is presented for a second major gene pool of influenza A viruses in nature. Shorebirds and gulls harbor influenza viruses when sampled in the spring and fall. Approximately half of the viruses isolated have the potential to infect ducks but the remainder do not. The hemagglutinin subtypes that are prevalent in wild ducks were rare or absent in shorebirds and gulls.
Influenza A/Turk/Wis/66 virus was studied in vivo. Virus isolations were attempted from tracheal swabs, and their relations to serum HI antibody levels were noted. Virus could be isolated from infected birds with low levels of antibody, and most birds had only low levels of antibody. Environmental factors appeared to play a very important part in infection and disease. Apparently recovered birds stressed by chilling could evidence further infection, as measured by virus isolation and rises in HI titers. Variation in the clinical aspects of the disease was considerable. These are classified as chronic, inapparent, and acute self-limiting.
An avian influenza virus with surface antigens similar to those of fowl plague virus (Hav 1 Nav 2) was isolated in 1979 from 2 commercial turkey flocks in Central Texas. Two flocks in contact with these infected flocks developed clinical signs, gross lesions, and seroconversion but yielded no virus. This was the first recorded incidence of clinical avian influenza in Texas turkeys and only the second time that an agent with these surface antigens was isolated from turkeys in U.S.
Two outbreaks of influenza were diagnosed in two turkey breeder flocks raised in consecutive years on an Ohio farm that also had a swine operation. The antibody detected indicated that the virus causing the disease had the Hswl hemagglutinin (swine influenza). Signs of disease onset were a decline in egg production and an increase in the number of abnormal eggs. Antibodies against the Hswl hemagglutinin were detected in swine raised on the farm.
Isolation-reared mallards (Anas platyrhynchos) were placed on ponds in turkey-rearing areas in Minnesota, and their cloacae were periodically swabbed to attempt isolating virus from embryonated chicken eggs. Nearby turkeys were sampled by taking cloacal and tracheal swabs as well as blood samples. Hemagglutinating viruses were identified at the National Veterinary Services Laboratory, U.S. Department of Agriculture, Ames, Iowa. During this two-year study, the weekly influenza virus-isolation rate from ducks varied from 0 to 24.4%. A total of 213 influenza viruses were isolated from the ducks. Twenty-six influenza virus subtypes were detected. Ninety-seven flocks of turkeys were diagnosed as having influenza by virus isolation and/or serology. Eight influenza virus subtypes were involved in the turkey outbreaks, and seven of these were also detected in the ducks and/or other avian species. The weekly infection rate of the sentinel ducks correlated directly with observations of wild ducks at the monitoring sites. Influenza virus was isolated from water samples collected near the sentinel duck sites during the study.
A longitudinal survey of viruses in feral ducks from 1976 to 1978 in the Vermillion area of Alberta, Canada, has shown that influenza A viruses and paramyxoviruses are present year after year in these apparently healthy ducks. Influenza viruses were isolated most frequently each year from mallards, pintails, and blue-winged teals, but were not restricted to these species. During the 3-year survey, 1262 influenza viruses were isolated from 4827 ducks, revealing the high incidence of influenza infection, a finding which contrasts with the very low incidence found in ducks during migration through Tennessee. Many different influenza A viruses were detected in the ducks, including 27 different combinations of hemagglutinin and neuraminidase subtypes. These viruses encompass all but one of the known hemagglutinin and neuraminidase subtypes. The virus subtypes in the ducks varied from year to year; however, 6 of these 27 subtypes were present every year. The predominant subtype changed from Hav7Neq2 in 1976-1977 to Hav6N2 in 1978. Antigenic comparisons of current and previous Hav6 viruses isolated from ducks, turkeys, and a shearwater showed that antigenic drift occurs in avian influenza viruses. Paramyxoviruses occur in the Canadian ducks at a much lower frequency than influenza viruses; in 3 years, 69 paramyxoviruses were isolated and included two types: lentogenic NDV and Duck/Mississippi/75. These longitudinal studies indicate that the feral ducks in the study area of Canada are a perpetual reservoir of diverse influenza A viruses and paramyxoviruses.
To provide information on the mechanism of perpetuation of influenza viruses among waterfowl reservoirs in nature, virological surveillance was carried out in Alaska during their breeding season in summer from 1991 to 1994. Influenza viruses were isolated mainly from fecal samples of dabbling ducks in their nesting places in central Alaska. The numbers of subtypes of 108 influenza virus isolates were 1 H2N3, 37 H3N8, 55 H4N6, 1 H7N3, 1 H8N2, 1 H10N2, 11 H10N7, and H10N9. Influenza viruses were also isolated from water samples of the lakes where they nest. Even in September of 1994 when the most ducks had left for migration to south, viruses were still isolated from the lake water. Phylogenetic analysis of the NP genes of the representative isolates showed that they belong to the North American lineage of avian influenza viruses, suggesting that the majority of the waterfowls breeding in central Alaska migrate to North America and not to Asia. The present results support the notion that influenza viruses have been maintained in waterfowl population by water-borne transmission and revealed the mechanism of year-by-year perpetuation of the viruses in the lakes where they breed.
Avian influenza A viruses of the H5 and H7 subtypes periodically cause severe outbreaks of disease in poultry. The question we wished to address in this study is whether these highly pathogenic strains constitute unique lineages or whether they and related nonpathogenic viruses are derived from common ancestors in the wild bird reservoir. We therefore compared the nucleotide and amino acid sequences of the hemagglutinin (HA) genes of 15 H5 and 26 H7 influenza A viruses isolated over 91 years from a variety of host species in Eurasia, Africa, Australia, and North America. Phylogenetic analysis indicated that the HA genes of H5 and H7 viruses that cause severe disease in domestic birds do not form unique lineages but share common ancestors with nonpathogenic H5 and H7 viruses. These findings predict that highly pathogenic avian H5 and H7 influenza A viruses will continue to emerge from wild bird reservoirs. Another important question is whether H7 influenza viruses found in mammalian species are derived from avian strains. We included eight equine influenza viruses and one seal isolate in the phylogenetic analysis of H7 HA genes. We could show that the HA genes of both, the equine and the seal viruses, shared ancestors with avian H7 HA genes. This indicates that currently circulating H7 viruses with an avian HA gene may have the potential to adapt to mammalian species and to cause an influenza outbreak in the new host.