Quantifying Transmission of Highly Pathogenic and Low Pathogenicity H7N1 Avian Influenza in Turkeys

Outbreaks of avian influenza in poultry can be devastating, yet many of the basic epidemiological parameters have not been accurately characterised. In 1999–2000 in Northern Italy, outbreaks of H7N1 low pathogenicity avian influenza virus (LPAI) were followed by the emergence of H7N1 highly pathogenic avian influenza virus (HPAI). This study investigates the transmission dynamics in turkeys of representative HPAI and LPAI H7N1 virus strains from this outbreak in an experimental setting, allowing direct comparison of the two strains. The fitted transmission rates for the two strains are similar: 2.04 (1.5–2.7) per day for HPAI, 2.01 (1.6–2.5) per day for LPAI. However, the mean infectious period is far shorter for HPAI (1.47 (1.3–1.7) days) than for LPAI (7.65 (7.0–8.3) days), due to the rapid death of infected turkeys. Hence the basic reproductive ratio, is significantly lower for HPAI (3.01 (2.2–4.0)) than for LPAI (15.3 (11.8–19.7)). The comparison of transmission rates and are critically important in relation to understanding how HPAI might emerge from LPAI. Two competing hypotheses for how transmission rates vary with population size are tested by fitting competing models to experiments with differing numbers of turkeys. A model with frequency-dependent transmission gives a significantly better fit to experimental data than density-dependent transmission. This has important implications for extrapolating experimental results from relatively small numbers of birds to the commercial poultry flock size, and for how control, including vaccination, might scale with flock size.     

A Cross-Sectional Study of Avian Influenza in One District of Guangzhou, 2013

Since Feb, 2013, more than 100 human beings had been infected with novel H7N9 avian influenza virus. As of May 2013, several H7N9 viruses had been found in retail live bird markets (LBMs) in Guangdong province of southern China where several human cases were confirmed later. However, the real avian influenza virus infection status especially H7N9 in Guangzhou remains unclear. Therefore, a cross-sectional study of avian influenza in commercial poultry farms, the wholesale LBM and retail LBMs in one district of Guangzhou was conducted from October to November, 2013. A total of 1505 cloacal and environmental samples from 52 commercial poultry farms, 1 wholesale LBM and 18 retail LBMs were collected and detected using real-time RT-PCR for type A, H7, H7N9 and H9 subtype avian influenza virus, respectively. Of all the flocks randomly sampled, 6 farms, 12 vendors of the wholesale LBM and 18 retail LBMs were type A avian influenza virus positive with 0, 3 and 11 positive for H9, respectively. The pooled prevalence and individual prevalence of type A avian influenza virus were 33.9% and 7.9% which for H9 subtype was 7.6% and 1.6%, respectively. None was H7 and H7N9 subtype virus positive. Different prevalence and prevalence ratio were found in different poultry species with partridges having the highest prevalence for both type A and H9 subtype avian influenza virus. Our results suggest that LBM may have a higher risk for sustaining and transmission of avian influenza virus than commercial poultry farms. The present study also indicates that different species may play different roles in the evolution and transmission of avian influenza virus. Therefore, risk-based surveillance and management measures should be conducted in future in this area.     

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.     

Prevention of avian influenza epidemic: what policy should we choose?

Human-to-human transmission of the avian influenza has been extremely rarely reported, and is considered as limited, inefficient and unsustained. However, experts warn an occurrence of “mutant avian influenza”, which can easily spread among humans, because the avian influenza is already endemic, in particular in Asian poultry, and it is evolving in domestic and wild birds, pigs and humans. Outbreak of such mutant avian influenza in the human world may have devastating consequences, which are comparable with these for the 1918 “Spanish influenza”. In this paper we develop a mathematical model for the spread of the mutant avian influenza, and explore the effectivity of the prevention policies, namely the elimination policy which increases the effective additional death rate of the infected birds and the quarantine policy which reduces the number of infective contacts.     

The evolutionary emergence of pandemic influenza

Pandemic influenza remains a serious public health threat and the processes involved in the evolutionary emergence of pandemic influenza strains remain incompletely understood. Here, we develop a stochastic model for the evolutionary emergence of pandemic influenza, and use it to address three main questions. (i) What is the minimum annual number of avian influenza virus infections required in humans to explain the historical rate of pandemic emergence? (ii) Are such avian influenza infections in humans more likely to give rise to pandemic strains if they are driven by repeated cross-species introductions, or by low-level transmission of avian influenza viruses between humans? (iii) What are the most effective interventions for reducing the probability that an influenza strain with pandemic potential will evolve? Our results suggest that if evolutionary emergence of past pandemics has occurred primarily through viral reassortment in humans, then thousands of avian influenza virus infections in humans must have occurred each year for the past 250 years. Analyses also show that if there is epidemiologically significant variation among avian influenza virus genotypes, then avian virus outbreaks stemming from repeated cross-species transmission events result in a greater likelihood of a pandemic strain evolving than those caused by low-level transmission between humans. Finally, public health interventions aimed at reducing the duration of avian virus infections in humans give the greatest reduction in the probability that a pandemic strain will evolve.     

A mathematical model of avian influenza with half-saturated incidence

The widespread impact of avian influenza viruses not only poses risks to birds, but also to humans. The viruses spread from birds to humans and from human to human In addition, mutation in the primary strain will increase the infectiousness of avian influenza. We developed a mathematical model of avian influenza for both bird and human populations. The effect of half-saturated incidence on transmission dynamics of the disease is investigated. The half-saturation constants determine the levels at which birds and humans contract avian influenza. To prevent the spread of avian influenza, the associated half-saturation constants must be increased, especially the half-saturation constant H _m for humans with mutant strain. The quantity H _m plays an essential role in determining the basic reproduction number of this model. Furthermore, by decreasing the rate β _m at which human-to-human mutant influenza is contracted, an outbreak can be controlled more effectively. To combat the outbreak, we propose both pharmaceutical (vaccination) and non-pharmaceutical (personal protection and isolation) control methods to reduce the transmission of avian influenza. Vaccination and personal protection will decrease β _m, while isolation will increase H _m. Numerical simulations demonstrate that all proposed control strategies will lead to disease eradication; however, if we only employ vaccination, it will require slightly longer to eradicate the disease than only applying non-pharmaceutical or a combination of pharmaceutical and non-pharmaceutical control methods. In conclusion, it is important to adopt a combination of control methods to fight an avian influenza outbreak.     

Biosecurity Conditions in Small Commercial Chicken Farms,Bangladesh 2011–2012

In Bangladesh, highly pathogenic avian influenza H5N1 is endemic in poultry. This study aimed to understand the biosecurity conditions and farmers’ perception of avian influenza biosecurity in Bangladeshi small commercial chicken farms. During 2011–2012, we conducted observations, in-depth interviews and group discussions with poultry farmers in 16 farms and in-depth interviews with seven local feed vendors from two districts. None of the farms were completely segregated from people, backyard poultry, other animals, households, other poultry farms or large trees. Wild birds and rodents accessed the farms for poultry feed. Farmers usually did not allow the buyers to bring egg trays inside their sheds. Spraying disinfectant in the shed and removing feces were the only regular cleaning and disinfection activities observed. All farmers sold or used untreated feces as fish feed or fertilizer. Farmers were more concerned about Newcastle disease and infectious bursal disease than about avian influenza. Farmers’ understanding about biosecurity and avian influenza was influenced by local vendors. While we seldom observed flock segregation, some farmers used measures that involved additional cost or effort to protect their flocks. These farmers could be motivated by interventions to protect their investment from diseases they consider harmful. Future interventions could explore the feasibility and effectiveness of low-cost alternative biosecurity measures.     

Poultry Slaughtering Practices in Rural Communities of Bangladesh and Risk of Avian Influenza Transmission: A Qualitative Study

Slaughtering sick poultry is a risk factor for human infection with highly pathogenic avian influenza and is a common practice in Bangladesh. This paper describes human exposures to poultry during slaughtering process and the customs and rituals influencing these practices in two Bangladeshi rural communities. In 2009, we conducted 30 observations to observe slaughtering practices and 110 in-depth and short interviews and 36 group discussions to explore reasons behind those practices. The villagers reported slaughtering 103 poultry, including 20 sick poultry during 2 months. During different stages of slaughtering, humans, the environment, healthy poultry, and other animals were exposed to poultry blood and body parts. Women performed most of the slaughtering tasks, including evisceration. Defeathering required the most time and involved several persons. During festivals, ceremonies, and rituals, many people gathered and participated in the slaughtering of poultry. Exposure to poultry slaughtering created numerous opportunities for potential avian influenza transmission. Strategies that can be further tested to determine if they reduce the risk of transmission include skinning the carcasses of sick poultry, using hot water for defeathering and cleaning, using a bucket to contain slaughtering blood and carcass, burying the offal and encouraging handwashing.     

禽流感与猪流感病毒：跨越物种传播的新认识

今年在墨西哥暴发的流感疫情来源于一种新的流感病毒：甲型H1N1病毒．这种病毒包括人源,禽源和猪源等甲型流感病毒基因片段,为混合毒株．比较了禽、猪和人的流感病毒在其天然宿主中的致病机理,主要目的是评估猪和禽的流感病毒成为人兽共患病的可能性,同时还评估猪在禽流感病毒传入人的过程中可能起到的作用．禽流感和猪流感作为人畜共患疾病,在流感病毒从动物到人的传播过程中起到关键的作用．猪作为流感病毒的中间宿主,具有混合器作用,人、猪、禽流感病毒可在其体内进行基因重排产生新病毒,并可能跨越种间屏障感染人类．但是流感病毒本身的跨越种间障碍传播不足以引起人流感的大暴发,动物流感病毒必须经过显著的遗传变异后才能使其在人群中长期存在．     

H5N1禽流感的威胁与全球应对

当前H5N1禽流感在迁徙禽类、家禽中的暴发,以及越来越多的人感染病例的发生,使流感全球大流行的可能性持续存在。简要综述了H5N1禽流感在鸟类和其他动物中的暴发情况,H5N1禽流感的人感染病例,以及全球禽流感应对计划及疫苗、药物、病原体基础研究的进展。     

Novel H7N7 avian influenza viruses detected in migratory wild birds in eastern China between 2018 and 2020

Wild birds are the natural reservoirs of avian influenza viruses, and surveillance and assessment of these viruses in wild birds provide valuable information for early warning and control of animal diseases. In this study, we isolated 19 H7N7 avian influenza viruses from wild bird between 2018 and 2020. Full genomic analysis revealed that these viruses bear a single basic amino acid in the cleavage site of their hemagglutinin gene, and formed four different genotypes by actively reassorting other avian influenza viruses circulating in wild birds and ducks. The H7N7 viruses bound to both avian-type and human-type receptors, although their affinity for human-type receptors was markedly lower than that for avian-type receptors. Moreover, we found that the H7N7 viruses could replicate efficiently in the upper respiratory tract and caecum of domestic ducks, and that the H5/H7 inactivated vaccine used in poultry in China provided complete protection against H7N7 wild bird virus challenge in ducks. Our findings demonstrate that wild bird H7N7 viruses pose a substantial threat to the poultry industry across the East Asian-Australian migratory flyway, emphasize the importance of influenza virus surveillance in both wild and domestic birds, and support the development of active control strategies against H7N7 virus.     

人感染H7亚型禽流感事件

本研究综述了自1959年以来国内外发生的人感染H7亚型禽流感事件。大多数是在家禽爆发禽流感期间,农场工人在处置感染鸡群过程中被暴露而感染;也有曾接触活禽或曾到过活禽市场而感染;有经禽流感病毒致病的哺乳动物（海豹）感染于人或实验室感染（事故）所致。引起人感染的H7亚型中已知有H7N2、H7N3、H7N7以及2013年在中国发现的新的致病亚型H7N9。H7N2、H7N3、H7N7感染以结膜炎为主,大多为轻症;而H7N9感染以严重的呼吸道感染为特征,表现为重症肺炎,呼吸窘迫综合症,病死率高达33.6%。     

Investigation of avian influenza virus in poultry and wild birds due to novel avian-origin influenza A(H10N8) in Nanchang City,China

Multiple reassortment events within poultry and wild birds had resulted in the establishment of another novel avian influenza A(H10N8) virus, and finally resulted in human death in Nanchang, China. However, there was a paucity of information on the prevalence of avian influenza virus in poultry and wild birds in Nanchang area. We investigated avian influenza virus in poultry and wild birds from live poultry markets, poultry countyards, delivery vehicles, and wild-bird habitats in Nanchang. We analyzed 1036 samples from wild birds and domestic poultry collected from December 2013 to February 2014. Original biological samples were tested for the presence of avian influenza virus using specific primer and probe sets of H5, H7, H9, H10 and N8 subtypes by real-time RT-PCR. In our analysis, the majority (97.98%) of positive samples were from live poultry markets. Among the poultry samples from chickens and ducks, AIV prevalence was 26.05 and 30.81%, respectively. Mixed infection of different HA subtypes was very common. Additionally, H10 subtypes coexistence with N8 was the most prevalent agent during the emergence of H10N8. This event illustrated a long-term surveillance was so helpful for pandemic preparedness and response.     

Evolutionary Repercussions of Avian Culling on Host Resistance and Influenza Virulence

Background

Keeping pandemic influenza at bay is a global health priority. Of particular concern is the continued spread of the influenza subtype H5N1 in avian populations and the increasing frequency of transmission to humans. To decrease this threat, mass culling is the principal strategy for eradicating influenza in avian populations. Although culling has a crucial short-term epidemiological benefit, evolutionary repercussions on reservoir hosts and on the viral population have not been considered.

Methods and Findings

To explore the epidemiological and evolutionary repercussions of mass avian culling, we combine population genetics and epidemiological influenza dynamics in a mathematical model parameterized by clinical, epidemiological, and poultry data. We model the virulence level of influenza and the selection on a dominant allele that confers resistance against influenza [1], [2] in a poultry population. Our findings indicate that culling impedes the evolution of avian host resistance against influenza. On the pathogen side of the coevolutionary race between pathogen and host, culling selects for heightened virulence and transmissibility of influenza.

Conclusions

Mass culling achieves a short-term benefit at the expense of long-term detriments: a more genetically susceptible host population, ultimately greater mortality, and elevated influenza virulence.     

Characterization of a human H5N1 influenza A virus isolated in 2003

In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.     

禽流感及其免疫防制研究

禽流感一直是严重危害世界各国养禽业发展的头号大敌,近期又成为继严重急性呼吸道综合症(SARS)后又一严重威胁人类生命安全的重要疾病,由于禽流感病毒抗原及其致病力的易变性,这就要求未来的防制策略要采取快速检测,并用先进的分子生物学技术进行病毒鉴定、检疫及免疫保护等措施,建立全国性甚至全球性禽流感检测防制网络,并且搞清禽流感与人类流感的关系,从而保证人和动物的安全.     

Evidence of infection with H4 and H11 avian influenza viruses among Lebanese chicken growers

Human infections with H5, H7, and H9 avian influenza viruses are well documented. Exposure to poultry is the most important risk factor for humans becoming infected with these viruses. Data on human infection with other low pathogenicity avian influenza viruses is sparse but suggests that such infections may occur. Lebanon is a Mediterranean country lying under two major migratory birds flyways and is home to many wild and domestic bird species. Previous reports from this country demonstrated that low pathogenicity avian influenza viruses are in circulation but highly pathogenic H5N1 viruses were not reported. In order to study the extent of human infection with avian influenza viruses in Lebanon, we carried out a seroprevalence cross-sectional study into which 200 poultry-exposed individuals and 50 non-exposed controls were enrolled. We obtained their sera and tested it for the presence of antibodies against avian influenza viruses types H4 through H16 and used a questionnaire to collect exposure data. Our microneutralization assay results suggested that backyard poultry growers may have been previously infected with H4 and H11 avian influenza viruses. We confirmed these results by using a horse red blood cells hemagglutination inhibition assay. Our data also showed that farmers with antibodies against each virus type clustered in a small geographic area suggesting that unrecognized outbreaks among birds may have led to these human infections. In conclusion, this study suggests that occupational exposure to chicken is a risk factor for infection with avian influenza especially among backyard growers and that H4 and H11 influenza viruses may possess the ability to cross the species barrier to infect humans.     

Avian-human influenza epidemic model

A mathematical model is proposed to interpret the spread of avian influenza from the bird world to the human world. Our mathematical model warns that two types of the outbreak of avian influenza may occur if the humans do not prevent the spread of avian influenza. Moreover, it suggests that we cannot feel relieved although the total infected humans are kept at low level. In order to prevent spread of avian influenza in the human world, we must take the measures not only for the birds infected with avian influenza to exterminate but also for the humans infected with mutant avian influenza to quarantine when mutant avian influenza has already occurred. In particular, the latter measure is shown to be important to stop the second pandemic of avian influenza.     

Avian influenza H5N1: an update on molecular pathogenesis

Avian influenza A virus constitutes a large threat to human health. Recent outbreaks of highly pathogenic avian influenza H5N1 virus in poultry and in humans have raised concerns that an influenza pandemic will occur in the near future. Transmission from avian species to humans remains sporadic, but the mortality associated with human infection is very high (about 62%). To date, there are no effective therapeutic drugs or a prophylactic vaccines available, which means that there is still a long way to go before we can eradicate or cure avian influenza. This review focuses on the molecular pathogenesis of avian influenza H5N1 virus infection. An understanding of the viral pathogenesis may facilitate the development of novel treatments or effective eradication of this fatal disease.     

Antigenic drift in H5N1 avian influenza virus in poultry is driven by mutations in major antigenic sites of the hemagglutinin molecule analogous to those for human influenza virus

H5N1 highly pathogenic avian influenza virus has been endemic in poultry in Egypt since 2008, notwithstanding the implementation of mass vaccination and culling of infected birds. Extensive circulation of the virus has resulted in a progressive genetic evolution and an antigenic drift. In poultry, the occurrence of antigenic drift in avian influenza viruses is less well documented and the mechanisms remain to be clarified. To test the hypothesis that H5N1 antigenic drift is driven by mechanisms similar to type A influenza viruses in humans, we generated reassortant viruses, by reverse genetics, that harbored molecular changes identified in genetically divergent viruses circulating in the vaccinated population. Parental and reassortant phenotype viruses were antigenically analyzed by hemagglutination inhibition (HI) test and microneutralization (MN) assay. The results of the study indicate that the antigenic drift of H5N1 in poultry is driven by multiple mutations primarily occurring in major antigenic sites at the receptor binding subdomain, similarly to what has been described for human influenza H1 and H3 subtype viruses.