Investigating Vietnam��s Ornamental Bird Trade: Implications for Transmission of Zoonoses

Global wildlife trade is financially lucrative, frequently illegal and increases the risk for zoonotic disease transmission. This paper presents the first interdisciplinary study of Vietnam’s illegal wild bird trade focussing on those aspects which may contribute to the transmission of diseases such as Highly Pathogenic Avian Influenza (HPAI) H5N1. Comparing January 2009 data with that of May 2007, we found a five-fold increase to 9,117 birds on sale in Hanoi. Ninety-five percent of Hanoian bird vendors appear unaware of trade regulations and across Vietnam vendors buy birds sourced outside of their province. Approximately 25% of the species common to Vietnam’s bird trade are known to be HPAI H5N1 susceptible. The anthropogenic movement of birds within the trade chain and the range of HPAI-susceptible species, often traded alongside poultry, increase the risk Vietnam’s bird trade presents for the transmission of pathogens such as HPAI H5N1. These results will assist in the control and monitoring of emerging zoonotic diseases and conservation of Southeast Asia’s avifauna.     

Highly pathogenic avian influenza is an emerging disease threat to wild birds in North America

Prior to the emergence of the A/goose/Guangdong/1/1996 (Gs/GD) H5N1 influenza A virus, the long-held and well-supported paradigm was that highly pathogenic avian influenza (HPAI) outbreaks were restricted to poultry, the result of cross-species transmission of precursor viruses from wild aquatic birds that subsequently gained pathogenicity in domestic birds. Therefore, management agencies typically adopted a prevention, control, and eradication strategy that included strict biosecurity for domestic bird production, isolation of infected and exposed flocks, and prompt depopulation. In most cases, this strategy has proved sufficient for eradicating HPAI. Since 2002, this paradigm has been challenged with many detections of viral descendants of the Gs/GD lineage among wild birds, most of which have been associated with sporadic mortality events. Since the emergence and evolution of the genetically distinct clade 2.3.4.4 Gs/GD lineage HPAI viruses in approximately 2010, there have been further increases in the occurrence of HPAI in wild birds and geographic spread through migratory bird movement. A prominent example is the introduction of clade 2.3.4.4 Gs/GD HPAI viruses from East Asia to North America via migratory birds in autumn 2014 that ultimately led to the largest outbreak of HPAI in the history of the United States. Given the apparent maintenance of Gs/GD lineage HPAI viruses in a global avian reservoir; bidirectional virus exchange between wild and domestic birds facilitating the continued adaptation of Gs/GD HPAI viruses in wild bird hosts; the current frequency of HPAI outbreaks in wild birds globally, and particularly in Eurasia where Gs/GD HPAI viruses may now be enzootic; and ongoing dispersal of AI viruses from East Asia to North America via migratory birds, HPAI now represents an emerging disease threat to North American wildlife. This recent paradigm shift implies that management of HPAI in domestic birds alone may no longer be sufficient to eradicate HPAI viruses from a given country or region. Rather, agencies managing wild birds and their habitats may consider the development or adoption of mitigation strategies to minimize introductions to poultry, to reduce negative impacts on wild bird populations, and to diminish adverse effects to stakeholders using wildlife resources. The main objective of this review is, therefore, to provide information that will assist wildlife managers in developing mitigation strategies or approaches for dealing with outbreaks of Gs/GD HPAI in wild birds in the form of preparedness, surveillance, research, communications, and targeted management actions. Resultant outbreak response plans and actions may represent meaningful steps of wildlife managers toward the use of collaborative and multi-jurisdictional One Health approaches when it comes to the detection, investigation, and mitigation of emerging viruses at the human-domestic animal-wildlife interface.     

An Exploration of How Perceptions of the Risk of Avian Influenza in Poultry Relate to Urbanization in Vietnam

This research examined how perceptions of outbreaks of highly pathogenic avian influenza (HPAI) subtype H5N1 in poultry are related to urbanization. Via in-depth interviews with village leaders, household farmers, and large farm operators in modern, transitional, and traditional communes in the north of Vietnam, we explored behaviors, attitudes, cultural values, and traditions that might amplify or attenuate HPAI outbreaks. We also explored conceptualizations of urbanization and its impacts on animal husbandry and disease outbreaks. Qualitative theme analyses identified the key impacts, factors related to HPAI outbreaks, and disease prevention and management strategies. The analyses also highlighted how urbanization improves some aspects of life (e.g., food security, family wealth and health, more employment opportunities, and improved infrastructure), but simultaneously poses significant challenges for poultry farming and disease management. Awareness of qualitative aspects of HPAI risk perceptions and behaviors and how they vary with urbanization processes may help to improve the prevention and management of emerging infectious diseases.     

Avian influenza viruses isolated in Japan

Currently, H5N1 influenza viruses remain a serious public health concern in Asia and now in Europe. We showed that the H5N1 viruses associated with outbreaks of HPAI in chickens in Japan were genotypically closely related to an H5N1 virus isolated from a chicken in China in 2003 (genotype V), but were different from those prevalent in southeastern Asia in 2003-2004 (i.e., genotype Z). H5N1 viruses were also isolated from duck meat imported from China during this routine surveillance in May of 2003. We characterized these H5N1 isolates and found that poultry products contaminated with influenza viruses of high pathogenic potential to mammals are a threat to public health even in countries where the virus is not enzootic and represent a possible source of influenza outbreaks in poultry.     

Seroprevalence of Antibodies to Highly Pathogenic Avian Influenza A (H5N1) Virus among Close Contacts Exposed to H5N1 Cases,China, 2005–2008

To assess the extent of highly pathogenic avian influenza (HPAI) A (H5N1) virus transmission, we conducted sero-epidemiologic studies among close contacts exposed to H5N1 cases in mainland China during 2005–2008. Blood specimens were collected from 87 household members and 332 social contacts of 23 H5N1 index cases for HPAI H5N1 serological testing by modified horse red-blood-cell hemagglutinin inhibition and microneutralization assays. All participants were interviewed with a standardized questionnaire to collect information about the use of personal protective equipment, illness symptoms, exposure to an H5N1 case during the infectious period, and poultry exposures. Two (2.3%) household contacts tested positive for HPAI H5N1 virus antibody, and all social contacts tested negative. Both seropositive cases had prolonged, unprotected, close contact with a different H5N1 index case, including days of bed-care or sleeping together during the index case’s infectious period, and did not develop any illness. None of the 419 close contacts used appropriate personal protective equipment including 17% who reported providing bedside care or having physical contact with an H5N1 case for at least 12 hours. Our findings suggest that HPAI H5N1 viruses that circulated among poultry in mainland China from 2005–2008 were not easily transmitted to close contacts of H5N1 cases.     

Flying Over an Infected Landscape: Distribution of Highly Pathogenic Avian Influenza H5N1 Risk in South Asia and Satellite Tracking of Wild Waterfowl

Highly pathogenic avian influenza (HPAI) H5N1 virus persists in Asia, posing a threat to poultry, wild birds, and humans. Previous work in Southeast Asia demonstrated that HPAI H5N1 risk is related to domestic ducks and people. Other studies discussed the role of migratory birds in the long distance spread of HPAI H5N1. However, the interplay between local persistence and long-distance dispersal has never been studied. We expand previous geospatial risk analysis to include South and Southeast Asia, and integrate the analysis with migration data of satellite-tracked wild waterfowl along the Central Asia flyway. We find that the population of domestic duck is the main factor delineating areas at risk of HPAI H5N1 spread in domestic poultry in South Asia, and that other risk factors, such as human population and chicken density, are associated with HPAI H5N1 risk within those areas. We also find that satellite tracked birds (Ruddy Shelduck and two Bar-headed Geese) reveal a direct spatio-temporal link between the HPAI H5N1 hot-spots identified in India and Bangladesh through our risk model, and the wild bird outbreaks in May-June-July 2009 in China (Qinghai Lake), Mongolia, and Russia. This suggests that the continental-scale dynamics of HPAI H5N1 are structured as a number of persistence areas delineated by domestic ducks, connected by rare transmission through migratory waterfowl.     

Characterization of low-pathogenic H5 subtype influenza viruses from Eurasia: implications for the origin of highly pathogenic H5N1 viruses

Highly pathogenic avian influenza (HPAI) H5N1 viruses are now endemic in many Asian countries, resulting in repeated outbreaks in poultry and increased cases of human infection. The immediate precursor of these HPAI viruses is believed to be A/goose/Guangdong/1/96 (Gs/GD)-like H5N1 HPAI viruses first detected in Guangdong, China, in 1996. From 2000 onwards, many novel reassortant H5N1 influenza viruses or genotypes have emerged in southern China. However, precursors of the Gs/GD-like viruses and their subsequent reassortants have not been fully determined. Here we characterize low-pathogenic avian influenza (LPAI) H5 subtype viruses isolated from poultry and migratory birds in southern China and Europe from the 1970s to the 2000s. Phylogenetic analyses revealed that Gs/GD-like virus was likely derived from an LPAI H5 virus in migratory birds. However, its variants arose from multiple reassortments between Gs/GD-like virus and viruses from migratory birds or with those Eurasian viruses isolated in the 1970s. It is of note that unlike HPAI H5N1 viruses, those recent LPAI H5 viruses have not become established in aquatic or terrestrial poultry. Phylogenetic analyses revealed the dynamic nature of the influenza virus gene pool in Eurasia with repeated transmissions between the eastern and western extremities of the continent. The data also show reassortment between influenza viruses from domestic and migratory birds in this region that has contributed to the expanded diversity of the influenza virus gene pool among poultry in Eurasia.     

Comparison of Human and Animal Surveillance Data for H5N1 Influenza A in Egypt 2006–2011

Background

The majority of emerging infectious diseases are zoonotic (transmissible between animals and humans) in origin, and therefore integrated surveillance of disease events in humans and animals has been recommended to support effective global response to disease emergence. While in the past decade there has been extensive global surveillance for highly pathogenic avian influenza (HPAI) infection in both animals and humans, there have been few attempts to compare these data streams and evaluate the utility of such integration.

Methodology

We compared reports of bird outbreaks of HPAI H5N1 in Egypt for 2006–2011 compiled by the World Organisation for Animal Health (OIE) and the UN Food and Agriculture Organization (FAO) EMPRESi reporting system with confirmed human H5N1 cases reported to the World Health Organization (WHO) for Egypt during the same time period.

Principal Findings

Both human cases and bird outbreaks showed a cyclic pattern for the country as a whole, and there was a statistically significant temporal correlation between the data streams. At the governorate level, the first outbreak in birds in a season usually but not always preceded the first human case, and the time lag between events varied widely, suggesting regional differences in zoonotic risk and/or surveillance effectiveness. In a multivariate risk model, lower temperature, lower urbanization, higher poultry density, and the recent occurrence of a bird outbreak were associated with increased risk of a human case of HPAI in the same governorate, although the positive predictive value of a bird outbreak was low.

Conclusions

Integrating data streams of surveillance for human and animal cases of zoonotic disease holds promise for better prediction of disease risk and identification of environmental and regional factors that can affect risk. Such efforts can also point out gaps in human and animal surveillance systems and generate hypotheses regarding disease transmission.     

Success Factors for Avian Influenza Vaccine Use in Poultry and Potential Impact at the Wild Bird–Agricultural Interface

Thirty-two epizootics of high pathogenicity avian influenza (HPAI) have been reported in poultry and other birds since 1959. The ongoing H5N1 HPAI epizootic that began in 1996 has also spilled over to infect wild birds. Traditional stamping-out programs in poultry have resulted in eradication of most HPAI epizootics. However, vaccination of poultry was added as a control tool in 1995 and has been used during five epizootics. Over 113 billion doses of AI vaccine have been used in poultry from 2002 to 2010 as oil-emulsified, inactivated whole AIV vaccines (95.5%) and live vectored vaccines (4.5%). Over 99% of the vaccine has been used in the four H5N1 HPAI enzootic countries: China including Hong Kong (91%), Egypt (4.7%), Indonesia (2.3%), and Vietnam (1.4%) where vaccination programs have been nationwide and routine to all poultry. Ten other countries used vaccine in poultry in a focused, risk-based manner but this accounted for less than 1% of the vaccine used. Most vaccine “failures” have resulted from problems in the vaccination process; i.e., failure to adequately administer the vaccine to at-risk poultry resulting in lack of population immunity, while fewer failures have resulted from antigenic drift of field viruses away from the vaccine viruses. It is currently not feasible to vaccinate wild birds against H5N1 HPAI, but naturally occurring infections with H5 low pathogenicity avian influenza viruses may generate cross-protective immunity against H5N1 HPAI. The most feasible method to prevent and control H5N1 HPAI in wild birds is through control of the disease in poultry with use of vaccine to reduce environmental burden of H5N1 HPAIV, and eventual eradication of the virus in domestic poultry, especially in domestic ducks which are raised in enzootic countries on range or in other outdoor systems having contact with wild aquatic and periurban terrestrial birds.     

Evidence of infection by H5N2 highly pathogenic avian influenza viruses in healthy wild waterfowl

The potential existence of a wild bird reservoir for highly pathogenic avian influenza (HPAI) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses, responsible for concurrent outbreaks in migratory and domestic birds over Asia, Europe, and Africa. During a large-scale surveillance programme over Eastern Europe, the Middle East, and Africa, we detected avian influenza viruses of H5N2 subtype with a highly pathogenic (HP) viral genotype in healthy birds of two wild waterfowl species sampled in Nigeria. We monitored the survival and regional movements of one of the infected birds through satellite telemetry, providing a rare evidence of a non-lethal natural infection by an HP viral genotype in wild birds. Phylogenetic analysis of the H5N2 viruses revealed close genetic relationships with H5 viruses of low pathogenicity circulating in Eurasian wild and domestic ducks. In addition, genetic analysis did not reveal known gallinaceous poultry adaptive mutations, suggesting that the emergence of HP strains could have taken place in either wild or domestic ducks or in non-gallinaceous species. The presence of coexisting but genetically distinguishable avian influenza viruses with an HP viral genotype in two cohabiting species of wild waterfowl, with evidence of non-lethal infection at least in one species and without evidence of prior extensive circulation of the virus in domestic poultry, suggest that some strains with a potential high pathogenicity for poultry could be maintained in a community of wild waterfowl.     

Evolutionary dynamics and emergence of panzootic H5N1 influenza viruses

The highly pathogenic avian influenza (HPAI) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes, and also developed into multiple genetically distinct sublineages in China. From there, the virus has spread to over 60 countries. The ecological success of this virus in diverse species of both poultry and wild birds with frequent introduction to humans suggests that it is a likely source of the next human pandemic. Therefore, the evolutionary and ecological characteristics of its emergence from wild birds into poultry are of considerable interest. Here, we apply the latest analytical techniques to infer the early evolutionary dynamics of H5N1 virus in the population from which it emerged (wild birds and domestic poultry). By estimating the time of most recent common ancestors of each gene segment, we show that the H5N1 prototype virus was likely introduced from wild birds into poultry as a non-reassortant low pathogenic avian influenza H5N1 virus and was not generated by reassortment in poultry. In contrast, more recent H5N1 genotypes were generated locally in aquatic poultry after the prototype virus (A/goose/Guangdong/1/96) introduction occurred, i.e., they were not a result of additional emergence from wild birds. We show that the H5N1 virus was introduced into Indonesia and Vietnam 3-6 months prior to detection of the first outbreaks in those countries. Population dynamics analyses revealed a rapid increase in the genetic diversity of A/goose/Guangdong/1/96 lineage viruses from mid-1999 to early 2000. Our results suggest that the transmission of reassortant viruses through the mixed poultry population in farms and markets in China has selected HPAI H5N1 viruses that are well adapted to multiple hosts and reduced the interspecies transmission barrier of those viruses.     

Different Environmental Drivers of Highly Pathogenic Avian Influenza H5N1 Outbreaks in Poultry and Wild Birds

A large number of highly pathogenic avian influenza (HPAI) H5N1 outbreaks in poultry and wild birds have been reported in Europe since 2005. Distinct spatial patterns in poultry and wild birds suggest that different environmental drivers and potentially different spread mechanisms are operating. However, previous studies found no difference between these two outbreak types when only the effect of physical environmental factors was analysed. The influence of physical and anthropogenic environmental variables and interactions between the two has only been investigated for wild bird outbreaks. We therefore tested the effect of these environmental factors on HPAI H5N1 outbreaks in poultry, and the potential spread mechanism, and discussed how these differ from those observed in wild birds. Logistic regression analyses were used to quantify the relationship between HPAI H5N1 outbreaks in poultry and environmental factors. Poultry outbreaks increased with an increasing human population density combined with close proximity to lakes or wetlands, increased temperatures and reduced precipitation during the cold season. A risk map was generated based on the identified key factors. In wild birds, outbreaks were strongly associated with an increased Normalized Difference Vegetation Index (NDVI) and lower elevation, though they were similarly affected by climatic conditions as poultry outbreaks. This is the first study that analyses the differences in environmental drivers and spread mechanisms between poultry and wild bird outbreaks. Outbreaks in poultry mostly occurred in areas where the location of farms or trade areas overlapped with habitats for wild birds, whereas outbreaks in wild birds were mainly found in areas where food and shelters are available. The different environmental drivers suggest that different spread mechanisms might be involved: HPAI H5N1 spread to poultry via both poultry and wild birds, whereas contact with wild birds alone seems to drive the outbreaks in wild birds.     

Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong

The H5N1 avian influenza virus that killed 6 of 18 persons infected in Hong Kong in 1997 was transmitted directly from poultry to humans. Viral isolates from this outbreak may provide molecular clues to zoonotic transfer. Here we demonstrate that the H5N1 viruses circulating in poultry comprised two distinguishable phylogenetic lineages in all genes that were in very rapid evolution. When introduced into new hosts, influenza viruses usually undergo rapid alteration of their surface glycoproteins, especially in the hemagglutinin (HA). Surprisingly, these H5N1 isolates had a large proportion of amino acid changes in all gene products except in the HA. These viruses maybe reassortants each of whose HA gene is well adapted to domestic poultry while the rest of the genome arises from a different source. The consensus amino acid sequences of "internal" virion proteins reveal amino acids previously found in human strains. These human-specific amino acids may be important factors in zoonotic transmission.     

Genesis of pandemic influenza

During the last decade the number of reported outbreaks caused by highly pathogenic avian influenza (HPAI) in domestic poultry has drastically increased. At the same time, low pathogenic avian influenza (LPAI) strains, such as H9N2 in many parts of the Middle East and Asia and H6N2 in live bird markets in California, have become endemic. Each AI outbreak brings the concomitant possibility of poultry-to-human transmission. Indeed, human illness and death have resulted from such occasional transmissions with highly pathogenic avian H7N7 and H5N1 viruses while avian H9N2 viruses have been isolated from individuals with mild influenza. The transmission of avian influenza directly from poultry to humans has brought a sense of urgency in terms of understanding the mechanisms that lead to interspecies transmission of influenza. Domestic poultry species have been previously overlooked as potential intermediate hosts in the generation of influenza viruses with the capacity to infect humans. In this review, we will discuss molecular and epidemiological aspects that have led to the recurrent emergence of avian influenza strains with pandemic potential, with a particular emphasis on the current Asian H5N1 viruses.     

Susceptibility of wood ducks to H5N1 highly pathogenic avian influenza virus

Since 2002, H5N1 highly pathogenic avian influenza (HPAI) viruses have caused mortality in numerous species of wild birds; this is atypical for avian influenza virus (AIV) infections in these avian species, especially for species within the order Anseriformes. Although these infections document the susceptibility of wild birds to H5N1 HPAI viruses and the spillover of these viruses from infected domestic birds to wild birds, it is unknown whether H5N1 HPAI viruses can persist in free-living avian populations. In a previous study, we established that wood ducks (Aix sponsa) are highly susceptible to infection with H5N1 HPAI viruses. To quantify this susceptibility and further evaluate the likelihood of H5N1 HPAI viral maintenance in a wild bird population, we determined the concentration of virus required to produce infection in wood ducks. To accomplish this, 25 wood ducks were inoculated intranasally at 12-16 wk of age with decreasing concentrations of a H5N1 HPAI virus (A/Whooper Swan/Mongolia/244/05 [H5N1]). The median infectious dose and the lethal dose of H5N1 HPAI virus in wood ducks were very low (10(0.95) and 10(1.71) median embryo infectious dose [EID(50)]/ml, respectively) and less than that of chickens (10(2.80) and 10(2.80) EID(50)/ml). These results confirm that wood ducks are highly susceptible to infection with H5N1 HPAI virus. The data from this study, combined with what is known experimentally about H5N1 HPAI virus infection in wood ducks and viral persistence in aquatic environments, suggest that the wood duck would represent a sensitive indicator species for H5N1 HPAI. Results also suggest that the potential for decreased transmission efficiency associated with reduced viral shedding (especially from the cloaca) and a loss of environmental fitness (in water), may be offset by the ability of this virus to be transmitted through a very low infectious dose.     

Novel Reassortant Highly Pathogenic H5N2 Avian Influenza Viruses in Poultry in China

There has been multiple evidence that domestic poultry may act as a vessel for the generation of novel influenza A viruses. In this study, we have analyzed the evolution and pathogenicity of 4 H5N2 avian influenza viruses isolated from apparently healthy poultry from H5N1 virus endemic areas in China. Phylogenetic analysis revealed that two of these viruses, A/duck/Eastern China/1111/2011 (DK/EC/1111/11) and A/goose/Eastern China/1112/2011 (GS/EC/1112/11) were derived from reassortment events in which clade 2.3.4 highly pathogenic avian influenza (HPAI) H5N1 viruses acquired novel neuraminidase and nonstructural protein genes. Another two isolates, A/chicken/Hebei/1102/2010 (CK/HB/1102/10) and A/duck/Hebei/0908/2009 (DK/HB/0908/09), possess hemagglutinin (HA) gene belong to clade 7 H5 viruses and other genes from endemic H9N2 viruses, or from viruses of various subtypes of the natural gene pool. All of these H5N2 isolates bear characteristic sequences of HPAI virus at the cleavage site of HA, and animal experiments indicated that all of these viruses but DK/HB/0908/09 is highly pathogenic to chickens. In particular, DK/EC/1111/11 and GS/EC/1112/11 are also highly pathogenic to ducks and moderately pathogenic to mice. All of these 4 viruses were able to replicate in domestic ducks and mice without prior adaptation. The emergence of these novel H5N2 viruses adds more evidence for the active evolution of H5 viruses in Asia. The maintenance of the highly pathogenic phenotype of some of these viruses even after reassortment with a new NA subtypes, their ability to replicate and transmit in domestic poultry, and the pathogenicity in the mammalian mouse model, highlight the potential threat posed by these viruses to both veterinary and public health.     

Spatio-temporal data comparisons for global highly pathogenic avian influenza (HPAI) H5N1 outbreaks

Highly pathogenic avian influenza subtype H5N1 is a zoonotic disease and control of the disease is one of the highest priority in global health. Disease surveillance systems are valuable data sources for various researches and management projects, but the data quality has not been paid much attention in previous studies. Based on data from two commonly used databases (Office International des Epizooties (OIE) and Food and Agriculture Organization of the United Nations (FAO)) of global HPAI H5N1 outbreaks during the period of 2003-2009, we examined and compared their patterns of temporal, spatial and spatio-temporal distributions for the first time. OIE and FAO data showed similar trends in temporal and spatial distributions if they were considered separately. However, more advanced approaches detected a significant difference in joint spatio-temporal distribution. Because of incompleteness for both OIE and FAO data, an integrated dataset would provide a more complete picture of global HPAI H5N1 outbreaks. We also displayed a mismatching profile of global HPAI H5N1 outbreaks and found that the degree of mismatching was related to the epidemic severity. The ideas and approaches used here to assess spatio-temporal data on the same disease from different sources are useful for other similar studies.     

Rapid death of duck cells infected with influenza: a potential mechanism for host resistance to H5N1

Aquatic birds are the natural reservoir for most subtypes of influenza A, and a source of novel viruses with the potential to cause human pandemics, fatal zoonotic disease or devastating epizootics in poultry. It is well recognised that waterfowl typically show few clinical signs following influenza A infection, in contrast, terrestrial poultry such as chickens may develop severe disease with rapid death following infection with highly pathogenic avian influenza. This study examined the cellular response to influenza infection in primary cells derived from resistant (duck) and susceptible (chicken) avian hosts. Paradoxically, we observed that duck cells underwent rapid cell death following infection with low pathogenic avian H2N3, classical swine H1N1 and 'classical' highly pathogenic H5N1 viruses. Dying cells showed morphological features of apoptosis, increased DNA fragmentation and activation of caspase 3/7. Following infection of chicken cells, cell death occurred less rapidly, accompanied by reduced DNA fragmentation and caspase activation. Duck cells produced similar levels of viral RNA but less infectious virus, in comparison with chicken cells. Such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 fatal to ducks. The induction of rapid death in duck cells may be part of a mechanism of host resistance to influenza A, with the loss of this response leading to increased susceptibility to emergent strains of H5N1. These studies provide novel insights that should help resolve the long-standing enigma of host-pathogen relationships for highly pathogenic and zoonotic avian influenza.