Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China

H5N1 influenza A viruses are widely distributed among poultry in Asia, but until recently, only a limited number of wild birds were affected. During late April through June 2005, an outbreak of H5N1 virus infection occurred among wild birds at Qinghai Lake in China. Here, we describe the features of this outbreak. First identified in bar-headed geese, the disease soon spread to other avian species populating the lake. Sequence analysis of 15 viruses representing six avian species and collected at different times during the outbreak revealed four different H5N1 genotypes. Most of the isolates possessed lysine at position 627 in the PB2 protein, a residue known to be associated with virulence in mice and adaptation to humans. However, neither of the two index viruses possessed this residue. All of the viruses tested were pathogenic in mice, with the exception of one index virus. We also tested the replication of two viruses isolated during the Qinghai Lake outbreak and one unrelated duck H5N1 virus in rhesus macaques. The Qinghai Lake viruses did not replicate efficiently in these animals, producing no evidence of disease other than transient fever, while the duck virus replicated in multiple organs and caused symptoms of respiratory illness. Importantly, H5N1 viruses isolated in Mongolia, Russia, Inner Mongolia, and the Liaoning Province of China after August 2005 were genetically closely related to one of the genotypes isolated during the Qinghai outbreak, suggesting the dominant nature of this genotype and underscoring the need for worldwide intensive surveillance to minimize its devastating consequences.     

青海湖鸟岛斑头雁种群对H5N1亚型禽流感病毒的免疫状况

斑头雁（Anser indicus）是2005年青海湖H5N1型高致病性禽流感的主要被感染物种。为了解斑头雁目前对H5N1亚型禽流感病毒(AIV)免疫状况,2008年春季,在青海湖鸟岛采集该种群弃卵（68枚）和巢卵（125枚）,以血凝抑制试验（HI）检测抗H5N1亚型禽流感病毒的卵黄母源抗体（IgY）。根据测试结果推断,在高致病性禽流感暴发3年后,青海湖鸟岛繁殖的斑头雁种群有26.5%～35.2%的繁殖对可能已经获得了对H5N1型禽流感病毒的免疫能力。另外,以斑头雁巢密度和抗体效价进行相关分析发现,斑头雁母源抗体水平与斑头雁巢密度正相关(r=0.736, P=0.000),表明高密度繁殖群内的母源抗体传递更具有适应性意义。     

Eco-virological approach for assessing the role of wild birds in the spread of avian influenza H5N1 along the Central Asian Flyway

A unique pattern of highly pathogenic avian influenza (HPAI) H5N1 outbreaks has emerged along the Central Asia Flyway, where infection of wild birds has been reported with steady frequency since 2005. We assessed the potential for two hosts of HPAI H5N1, the bar-headed goose (Anser indicus) and ruddy shelduck (Tadorna tadorna), to act as agents for virus dispersal along this 'thoroughfare'. We used an eco-virological approach to compare the migration of 141 birds marked with GPS satellite transmitters during 2005-2010 with: 1) the spatio-temporal patterns of poultry and wild bird outbreaks of HPAI H5N1, and 2) the trajectory of the virus in the outbreak region based on phylogeographic mapping. We found that biweekly utilization distributions (UDs) for 19.2% of bar-headed geese and 46.2% of ruddy shelduck were significantly associated with outbreaks. Ruddy shelduck showed highest correlation with poultry outbreaks owing to their wintering distribution in South Asia, where there is considerable opportunity for HPAI H5N1 spillover from poultry. Both species showed correlation with wild bird outbreaks during the spring migration, suggesting they may be involved in the northward movement of the virus. However, phylogeographic mapping of HPAI H5N1 clades 2.2 and 2.3 did not support dissemination of the virus in a northern direction along the migration corridor. In particular, two subclades (2.2.1 and 2.3.2) moved in a strictly southern direction in contrast to our spatio-temporal analysis of bird migration. Our attempt to reconcile the disciplines of wild bird ecology and HPAI H5N1 virology highlights prospects offered by both approaches as well as their limitations.     

Satellite-marked waterfowl reveal migratory connection between H5N1 outbreak areas in China and Mongolia

The role of wild birds in the spread of highly pathogenic avian influenza H5N1 has been greatly debated and remains an unresolved question. However, analyses to determine involvement of wild birds have been hindered by the lack of basic information on their movements in central Asia. Thus, we initiated a programme to document migrations of waterfowl in Asian flyways to inform hypotheses of H5N1 transmission. As part of this work, we studied migration of waterfowl from Qinghai Lake, China, site of the 2005 H5N1 outbreak in wild birds. We examined the null hypothesis that no direct migratory connection existed between Qinghai Lake and H5N1 outbreak areas in central Mongolia, as suggested by some H5N1 phylogeny studies. We captured individuals in 2007 from two of the species that died in the Qinghai Lake outbreaks and marked them with GPS satellite transmitters: Bar-headed Geese Anser indicus ( n  =   14) and Ruddy Shelduck Tadorna ferruginea ( n  =   11). Three of 25 marked birds (one Goose and two Shelducks) migrated to breeding grounds near H5N1 outbreak areas in Mongolia. Our results describe a previously unknown migratory link between the two regions and offer new critical information on migratory movements in the region.     

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.     

The Survey of H5N1 Flu Virus in Wild Birds in 14 Provinces of China from 2004 to 2007

Background

The highly pathogenic H5N1 avian influenza emerged in the year 1996 in Asia, and has spread to Europe and Africa recently. At present, effective monitoring and data analysis of H5N1 are not sufficient in Chinese mainland.

Methodology/Principal Findings

During the period from April of 2004 to August of 2007, we collected 14,472 wild bird samples covering 56 species of 10 orders in 14 provinces of China and monitored the prevalence of flu virus based on RT-PCR specific for H5N1 subtype. The 149 positive samples involved six orders. Anseriformes had the highest prevalence while Passeriformes had the lowest prevalence (2.70% versus 0.36%). Among the 24 positive species, mallard (Anas platyrhynchos) had the highest prevalence (4.37%). A difference of prevalence was found among 14 provinces. Qinghai had a higher prevalence than the other 13 provinces combined (3.88% versus 0.43%). The prevalence in three species in Qinghai province (Pintail (Anas acuta), Mallard (Anas platyrhynchos) and Tufted Duck (Aythya fuligula)) were obviously higher than those in other 13 provinces. The results of sequence analysis indicated that the 17 strains isolated from wild birds were distributed in five clades (2.3.1, 2.2, 2.5, 6, and 7), which suggested that genetic diversity existed among H5N1 viruses isolated from wild birds. The five isolates from Qinghai came from one clade (2.2) and had a short evolutionary distance with the isolates obtained from Qinghai in the year 2005.

Conclusions/Significance

We have measured the prevalence of H5N1 virus in 56 species of wild birds in 14 provinces of China. Continuous monitoring in the field should be carried out to know whether H5N1 virus can be maintained by wild birds.     

Environmental factors contributing to the spread of H5N1 avian influenza in mainland China

Background

Since late 2003, highly pathogenic avian influenza (HPAI) outbreaks caused by infection with H5N1 virus has led to the deaths of millions of poultry and more than 10 thousands of wild birds, and as of 18-March 2008, at least 373 laboratory-confirmed human infections with 236 fatalities, have occurred. The unrestrained worldwide spread of this disease has caused great anxiety about the potential of another global pandemic. However, the effect of environmental factors influencing the spread of HPAI H5N1 virus is unclear.

Methodology/Principal Findings

A database including incident dates and locations was developed for 128 confirmed HPAI H5N1 outbreaks in poultry and wild birds, as well as 21 human cases in mainland China during 2004–2006. These data, together with information on wild bird migration, poultry densities, and environmental variables (water bodies, wetlands, transportation routes, main cities, precipitation and elevation), were integrated into a Geographical Information System (GIS). A case-control design was used to identify the environmental factors associated with the incidence of the disease. Multivariate logistic regression analysis indicated that minimal distance to the nearest national highway, annual precipitation and the interaction between minimal distance to the nearest lake and wetland, were important predictive environmental variables for the risk of HPAI. A risk map was constructed based on these factors.

Conclusions/Significance

Our study indicates that environmental factors contribute to the spread of the disease. The risk map can be used to target countermeasures to stop further spread of the HPAI H5N1 at its source.     

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.     

西藏南部羊卓雍错水鸟群落及斑头雁活动区域特征

2009年4月至2010年1月,对西藏南部羊卓雍错的水鸟资源状况进行了调查。采用定点观察的方法,沿湖选择了24个观察点,分别在繁殖前期、中期和后期,以及秋季和冬季进行了6次调查。采用核密度分析(Kernel analysis)的方法,对两只卫星跟踪斑头雁(Anser indicus)的活动区进行了分析。调查期间,记录到水鸟32种31044只,隶属于6目10科。雁鸭类和鸥类分别占水鸟总数73.9%和19.1%,主要是斑头雁、赤嘴潜鸭(Rhodonessa rufina)、赤麻鸭(Tadorna ferruginea)、棕头鸥(Larus brunnicephalus)等。水鸟多样性较高的季节是春秋迁徙季节。羊卓雍错夏季主要的繁殖种群是斑头雁和棕头鸥,也有少量黑颈鹤(Grus nigricollis)的繁殖个体;冬季主要物种是赤嘴潜鸭,经常聚集在融化的冰面上。春季斑头雁的数量增加趋势较为明显;进入繁殖期后,斑头雁处于孵卵阶段,繁殖种群的数量达到2000余只;繁殖后期,斑头雁换羽结束,成鸟带领幼鸟在鸟岛附近的湖边取食,此时观察到斑头雁的数量又有明显的增加;秋季斑头雁的南迁致使种群数量呈下降趋势;冬季许多斑头雁从北方如青海湖等地迁来越冬使得种群数量有所增加,多分布于湖西浪卡子县城附近的沼泽湿地和湖南部的绒波臧布河流的入口处。卫星跟踪结果表明,羊卓雍错是青海湖繁殖的斑头雁重要的越冬地之一,湖西部沼泽湿地和湖南部的河流入口处是其主要活动区域,而且该湖与雅鲁藏布江河谷之间通过斑头雁的往来移动存在着联系,因而是西藏南部禽流感监测的重要地点。     

Characterization of H5N1 Influenza Viruses That Continue To Circulate in Geese in Southeastern China

The H5N1 influenza virus, which killed humans and poultry in 1997, was a reassortant that possibly arose in one type of domestic poultry present in the live-poultry markets of Hong Kong. Given that all the precursors of H5N1/97 are still circulating in poultry in southern China, the reassortment event that generated H5N1 could be repeated. Because A/goose/Guangdong/1/96-like (H5N1; Go/Gd) viruses are the proposed donors of the hemagglutinin gene of the H5N1 virus, we investigated the continued circulation, host range, and transmissibility of Go/Gd-like viruses in poultry. The Go/Gd-like viruses caused weight loss and death in some mice inoculated with high virus doses. Transmission of Go/Gd-like H5N1 viruses to geese by contact with infected geese resulted in infection of all birds but limited signs of overt disease. In contrast, oral inoculation with high doses of Go/Gd-like viruses resulted in the deaths of up to 50% of infected geese. Transmission from infected geese to chickens occurred only by fecal contact, whereas transmission to quail occurred by either aerosol or fecal spread. This difference is probably explained by the higher susceptibility of quail to Go/Gd-like virus. The high degree of susceptibility of quail to Go/Gd (H5N1)-like viruses and the continued circulation of H6N1 and H9N2 viruses in quail support the hypothesis that quail were the host of origin of the H5N1/97 virus. The ease of transmission of Go/Gd (H5N1)-like viruses to land-based birds, especially quail, supports the wisdom of separating aquatic and land-based poultry in the markets in Hong Kong and the need for continued surveillance in the field and live-bird markets in which different types of poultry are in contact with one another.     

Phylogeography of Avian influenza A H9N2 in China

Background

During the past two decades, avian influenza A H9N2 viruses have spread geographically and ecologically in China. Other than its current role in causing outbreaks in poultry and sporadic human infections by direct transmission, H9N2 virus could also serve as an progenitor for novel human avian influenza viruses including H5N1, H7N9 and H10N8. Hence, H9N2 virus is becoming a notable threat to public health. However, despite multiple lineages and genotypes that were detected by previous studies, the migration dynamics of the H9N2 virus in China is unclear. Increasing such knowledge would help us better prevent and control H9N2 as well as other future potentially threatening viruses from spreading across China. The objectives of this study were to determine the source, migration patterns, and the demography history of avian influenza A H9N2 virus that circulated in China.

Results

Using Bayesian phylogeography framework, we showed that the H9N2 virus in mainland China may have originated from the Hong Kong Special Administrative Region (SAR). Southern China, most likely the Guangdong province acts as the primary epicentre for multiple H9N2 strains spreading across the whole country, and eastern China, most likely the Jiangsu province, acts as an important secondary source to seed outbreaks. Our demography inference suggests that during the long-term migration process, H9N2 evolved into multiple diverse lineages and then experienced a selective sweep, which reduced its genetic diversity. Importantly, such a selective sweep may pose a greater threat to public health because novel strains confer higher fitness advantages than strains being replaced and could generate new viruses through reassortment.

Conclusion

Our analyses indicate that migratory birds, poultry trade and transportation have all contributed to the spreading of the H9N2 virus in China. The ongoing migration and evolution of H9N2, which poses a constant threat to the human population, highlights the need for a more comprehensive surveillance of wild birds and for the enhancement of biosafety for China’s poultry industry.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1110) contains supplementary material, which is available to authorized users.     

Eurasian Tree Sparrows, risk for H5N1 virus spread and human contamination through Buddhist ritual: an experimental approach

Background

The Highly Pathogenic Avian Influenza H5N1 virus has dramatically spread throughout Southeast Asia since its first detection in 1997. Merit Release Birds, such as the Eurasian Tree Sparrow, are believed to increase one''s positive karma when kissed and released during Buddhist rituals. Since these birds are often in close contact with both poultry and humans, we investigated their potential role in the spread of H5N1 virus.

Methodology/Principal Findings

Seven series of experiments were conducted in order to investigate the possible interactions between inoculated and exposed birds, including sparrow/sparrow, sparrow/chicken, duck/sparrow. Daily and post-mortem samples collected were tested for H5N1 virus by real-time RT-PCR and egg inoculation. When directly inoculated, Eurasian Tree Sparrows were highly susceptible to the H5N1 virus, with a fatality rate approaching 100% within 5 days post-inoculation. Although transmission of fatal infection between sparrows did not occur, seroconversion of the exposed birds was observed. Up to 100% chickens exposed to inoculated sparrows died of H5N1 infection, depending on the caging conditions of the birds, while a fatality rate of 50% was observed on sparrows exposed to infected ducks. Large quantities of H5N1 virus were detected in the sparrows, particularly in their feathers, from which infectious particles were recovered.

Conclusions/Significance

Our study indicates that under experimental conditions, Eurasian Tree Sparrows are susceptible to H5N1 infection, either by direct inoculation or by contact with infected poultry. Their ability to transmit H5N1 infection to other birds is also demonstrated, suggesting that the sparrows may play a role in the dissemination of the virus. Finally, the presence of significant quantities of H5N1 virus on sparrows'' feathers, including infectious particles, would suggest that Merit Release Birds represent a risk for human contamination in countries where avian influenza virus is circulating and where this religious ritual is practiced.     

Recent expansion of highly pathogenic avian influenza H5N1: a critical review

Wild birds, particularly waterfowl, are a key element of the viral ecology of avian influenza. Highly pathogenic avian influenza (HPAI) virus, subtype H5N1, was first detected in poultry in November 1996 in southeast China, where it originated. The virus subsequently dispersed throughout most of Asia, and also to Africa and Europe. Despite compelling evidence that the virus has been dispersed widely via human activities that include farming, and marketing of poultry, migratory birds have been widely considered to be the primary source of its global dispersal. Here we present a critical examination of the arguments both for and against the role of migratory birds in the global dispersal of HPAI H5N1. We conclude that, whilst wild birds undoubtedly contribute to the local spread of the virus in the wild, human commercial activities, particularly those associated with poultry, are the major factors that have determined its global dispersal.     

Combining spatial-temporal and phylogenetic analysis approaches for improved understanding on global H5N1 transmission

Background

Since late 2003, the highly pathogenic influenza A H5N1 had initiated several outbreak waves that swept across the Eurasia and Africa continents. Getting prepared for reassortment or mutation of H5N1 viruses has become a global priority. Although the spreading mechanism of H5N1 has been studied from different perspectives, its main transmission agents and spread route problems remain unsolved.

Methodology/Principal Findings

Based on a compilation of the time and location of global H5N1 outbreaks from November 2003 to December 2006, we report an interdisciplinary effort that combines the geospatial informatics approach with a bioinformatics approach to form an improved understanding on the transmission mechanisms of H5N1 virus. Through a spherical coordinate based analysis, which is not conventionally done in geographical analyses, we reveal obvious spatial and temporal clusters of global H5N1 cases on different scales, which we consider to be associated with two different transmission modes of H5N1 viruses. Then through an interdisciplinary study of both geographic and phylogenetic analysis, we obtain a H5N1 spreading route map. Our results provide insight on competing hypotheses as to which avian hosts are responsible for the spread of H5N1.

Conclusions/Significance

We found that although South China and Southeast Asia may be the virus pool of avian flu, East Siberia may be the source of the H5N1 epidemic. The concentration of migratory birds from different places increases the possibility of gene mutation. Special attention should be paid to East Siberia, Middle Siberia and South China for improved surveillance of H5N1 viruses and monitoring of migratory birds.     

Virus isolation and molecular epidemiology of highly pathogenic avian influenza A(H5N8) from an outbreak in free-ranging wild birds,India 2016

We report the molecular epidemiology of highly pathogenic avian influenza (HPAI) virus involved in an outbreak causing death in free-ranging wild birds at Mysore, Karnataka state of India. The virus was typed as HPAI A(H5N8) by conventional and TaqMan probe based real-time PCR assays. Six isolates of HPAI virus were recovered in 9-day-old embryonated chicken eggs. Haemagglutinin gene-based phylogeny of virus isolates showed >?99.9% nucleotide sequence identity with HPAI A(H5N8) isolates from migratory birds and domestic poultry from China and Korea indicating either these wild birds have routed their migration through Korea and/or eastern China or these dead birds must have directly or indirectly contacted with wild birds migrating from Eastern China and/or Korean regions. The study emphasises the role of migratory wild birds in spread of HPAI across the globe.     

环青海湖斑头雁种群数量动态模拟及趋势分析

斑头雁是青海湖候鸟中的优势种之一,其未来种群数量的变化对青海湖的保护决策具有重要作用。利用STELLA图形化建模软件,从动力学出发,构建了青海湖地区斑头雁种群数量变化的动态模型。在该模型中,根据前人和青海湖自然保护区对斑头雁的观测研究结果,设置了班头雁的交配、产卵、孵卵、育幼、迁入、迁出、死亡等过程的模型参数。根据斑头雁在青海湖的活动时间,设置以年为模拟单位,选取1/7为模拟步长,对未来25年的青海湖斑头雁种群变化趋势进行了模拟,并进行了灾害模拟。模拟结果表明,未来青海湖斑头雁的最大种群数量,将在20 000余只的饱和数量之内变化。2006—2008年斑头雁观测数据验证表明,该模型模拟结果可信,其方法对青海湖的其他鸟类研究也具有一定的参考价值。     

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.     

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.     

Are Poultry or Wild Birds the Main Reservoirs for Avian Influenza in Bangladesh?

Avian influenza viruses (AIV) are of great socioeconomic and health concern, notably in Southeast Asia where highly pathogenic strains, such as highly pathogenic avian influenza (HPAI) H5N1 and other H5 and H7 AIVs, continue to occur. Wild bird migrants are often implicated in the maintenance and spread of AIV. However, little systematic surveillance of wild birds has been conducted in Southeast Asia to evaluate whether the prevalence of AIV in wild birds is higher than in other parts of the world where HPAI outbreaks occur less frequently. Across Bangladesh, we randomly sampled a total of 3585 wild and domestic birds to assess the prevalence of AIV and antibodies against AIV and compared these with prevalence levels found in other endemic and non-endemic countries. Our study showed that both resident and migratory wild birds in Bangladesh do not have a particularly elevated AIV prevalence and AIV sero-prevalence compared to wild birds from regions in the world where H5N1 is not endemic and fewer AIV outbreaks in poultry occur. Like elsewhere, notably wild birds of the orders Anseriformes were identified as the main wild bird reservoir, although we found exceptionally high sero-prevalence in one representative of the order Passeriformes, the house crow (Corvus splendens), importantly living on offal from live bird markets. This finding, together with high sero- and viral prevalence levels of AIV in domestic birds, suggests that wild birds are not at the base of the perpetuation of AIV problems in the local poultry sector, but may easily become victim to AIV spill back from poultry into some species of wild birds, potentially assisting in further spread of the virus.     

Highly pathogenic avian influenza (H5N1): pathways of exposure at the animal-human interface, a systematic review

Background

The threat posed by highly pathogenic avian influenza A H5N1 viruses to humans remains significant, given the continued occurrence of sporadic human cases (499 human cases in 15 countries) with a high case fatality rate (approximately 60%), the endemicity in poultry populations in several countries, and the potential for reassortment with the newly emerging 2009 H1N1 pandemic strain. Therefore, we review risk factors for H5N1 infection in humans.

Methods and Findings

Several epidemiologic studies have evaluated the risk factors associated with increased risk of H5N1 infection among humans who were exposed to H5N1 viruses. Our review shows that most H5N1 cases are attributed to exposure to sick poultry. Most cases are sporadic, while occasional limited human-to-human transmission occurs. The most commonly identified factors associated with H5N1 virus infection included exposure through contact with infected blood or bodily fluids of infected poultry via food preparation practices; touching and caring for infected poultry; consuming uncooked poultry products; exposure to H5N1 via swimming or bathing in potentially virus laden ponds; and exposure to H5N1 at live bird markets.

Conclusions

Research has demonstrated that despite frequent and widespread contact with poultry, transmission of the H5N1 virus from poultry to humans is rare. Available research has identified several risk factors that may be associated with infection including close direct contact with poultry and transmission via the environment. However, several important data gaps remain that limit our understanding of the epidemiology of H5N1 in humans. Although infection in humans with H5N1 remains rare, human cases continue to be reported and H5N1 is now considered endemic among poultry in parts of Asia and in Egypt, providing opportunities for additional human infections and for the acquisition of virus mutations that may lead to more efficient spread among humans and other mammalian species. Collaboration between human and animal health sectors for surveillance, case investigation, virus sharing, and risk assessment is essential to monitor for potential changes in circulating H5N1 viruses and in the epidemiology of H5N1 in order to provide the best possible chance for effective mitigation of the impact of H5N1 in both poultry and humans.

Disclaimer

The opinions expressed in this article are those of the authors and do not necessarily reflect those of the institutions or organizations with which they are affiliated.