The Contribution of Social Behaviour to the Transmission of Influenza A in a Human Population

Variability in the risk of transmission for respiratory pathogens can result from several factors, including the intrinsic properties of the pathogen, the immune state of the host and the host''s behaviour. It has been proposed that self-reported social mixing patterns can explain the behavioural component of this variability, with simulated intervention studies based on these data used routinely to inform public health policy. However, in the absence of robust studies with biological endpoints for individuals, it is unclear how age and social behaviour contribute to infection risk. To examine how the structure and nature of social contacts influenced infection risk over the course of a single epidemic, we designed a flexible disease modelling framework: the population was divided into a series of increasingly detailed age and social contact classes, with the transmissibility of each age-contact class determined by the average contacts of that class. Fitting the models to serologically confirmed infection data from the 2009 Hong Kong influenza A/H1N1p pandemic, we found that an individual''s risk of infection was influenced strongly by the average reported social mixing behaviour of their age group, rather than by their personal reported contacts. We also identified the resolution of social mixing that shaped transmission: epidemic dynamics were driven by intense contacts between children, a post-childhood drop in risky contacts and a subsequent rise in contacts for individuals aged 35–50. Our results demonstrate that self-reported social contact surveys can account for age-associated heterogeneity in the transmission of a respiratory pathogen in humans, and show robustly how these individual-level behaviours manifest themselves through assortative age groups. Our results suggest it is possible to profile the social structure of different populations and to use these aggregated data to predict their inherent transmission potential.     

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.     

Perceived Risk of Avian Influenza and Urbanization in Northern Vietnam

Decision-analytic models provide forecasts of how systems of interest will respond to management. These models can be parameterized using empirical data, but sometimes require information elicited from experts. When evaluating the effects of disease in species translocation programs, expert judgment is likely to play a role because complete empirical information will rarely be available. We illustrate development of a decision-analytic model built to inform decision-making regarding translocations and other management actions for the boreal toad (Anaxyrus boreas boreas), a species with declines linked to chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd). Using the model, we explored the management implications of major uncertainties in this system, including whether there is a genetic basis for resistance to pathogenic infection by Bd, how translocation can best be implemented, and the effectiveness of efforts to reduce the spread of Bd. Our modeling exercise suggested that while selection for resistance to pathogenic infection by Bd could increase numbers of sites occupied by toads, and translocations could increase the rate of toad recovery, efforts to reduce the spread of Bd may have little effect. We emphasize the need to continue developing and parameterizing models necessary to assess management actions for combating chytridiomycosis-associated declines.     

The Role of Environmental Transmission in Recurrent Avian Influenza Epidemics

Avian influenza virus (AIV) persists in North American wild waterfowl, exhibiting major outbreaks every 2–4 years. Attempts to explain the patterns of periodicity and persistence using simple direct transmission models are unsuccessful. Motivated by empirical evidence, we examine the contribution of an overlooked AIV transmission mode: environmental transmission. It is known that infectious birds shed large concentrations of virions in the environment, where virions may persist for a long time. We thus propose that, in addition to direct fecal/oral transmission, birds may become infected by ingesting virions that have long persisted in the environment. We design a new host–pathogen model that combines within-season transmission dynamics, between-season migration and reproduction, and environmental variation. Analysis of the model yields three major results. First, environmental transmission provides a persistence mechanism within small communities where epidemics cannot be sustained by direct transmission only (i.e., communities smaller than the critical community size). Second, environmental transmission offers a parsimonious explanation of the 2–4 year periodicity of avian influenza epidemics. Third, very low levels of environmental transmission (i.e., few cases per year) are sufficient for avian influenza to persist in populations where it would otherwise vanish.     

禽流感病毒与人流感的关系

禽流感病毒 (AIV)是甲 (A)型流感病毒 ,常引起禽类全身性感染或主要限于呼吸器官传染病 ,带来巨大的经济损失并严重威胁人类健康。对AIV的基因组、所编码的蛋白质及其功能、AIV毒力变异的分子基础、禽流感疫苗以及AIV与人流感的关系等进行概述。     

Ecological Routes of Avian Influenza Virus Transmission to a Common Mesopredator: An Experimental Evaluation of Alternatives

Background

Wild raccoons have been shown to be naturally exposed to avian influenza viruses (AIV). However, the mechanisms associated with these natural exposures are not well-understood.

Methodology/Principal Findings

We experimentally tested three alternative routes (water, eggs, and scavenged waterfowl carcasses) of AIV transmission that may explain how raccoons in the wild are exposed to AIV. Raccoons were exposed to 1) water and 2) eggs spiked with an AIV (H4N6), as well as 3) mallard carcasses experimentally inoculated with the same virus. Three of four raccoons exposed to the high dose water treatment yielded apparent nasal shedding of >10^2.0 PCR EID₅₀ equivalent/mL. Little to no shedding was observed from the fecal route. The only animals yielding evidence of serologic activity during the study period were three animals associated with the high dose water treatment.

Conclusions/Significance

Overall, our results indicate that virus-laden water could provide a natural exposure route of AIV for raccoons and possibly other mammals associated with aquatic environments. However, this association appears to be related to AIV concentration in the water, which would constitute an infective dose. In addition, strong evidence of infection was only detected in three of four animals exposed to a high dose (e.g., 10^5.0 EID₅₀/mL) of AIV in water. As such, water-borne transmission to raccoons may require repeated exposures to water with high concentrations of virus.     

The Role of Social Contacts and Original Antigenic Sin in Shaping the Age Pattern of Immunity to Seasonal Influenza

Recent serological studies of seasonal influenza A in humans suggest a striking characteristic profile of immunity against age, which holds across different countries and against different subtypes of influenza. For both H1N1 and H3N2, the proportion of the population seropositive to recently circulated strains peaks in school-age children, reaches a minimum between ages 35–65, then rises again in the older ages. This pattern is little understood. Variable mixing between different age classes can have a profound effect on disease dynamics, and is hence the obvious candidate explanation for the profile, but using a mathematical model of multiple influenza strains, we see that age dependent transmission based on mixing data from social contact surveys cannot on its own explain the observed pattern. Instead, the number of seropositive individuals in a population may be a consequence of ‘original antigenic sin’; if the first infection of a lifetime dominates subsequent immune responses, we demonstrate that it is possible to reproduce the observed relationship between age and seroprevalence. We propose a candidate mechanism for this relationship, by which original antigenic sin, along with antigenic drift and vaccination, results in the age profile of immunity seen in empirical studies.     

Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens

Despite considerable research efforts, little is yet known about key epidemiological parameters of H5N1 highly pathogenic influenza viruses in their avian hosts. Here we show how these parameters can be estimated using a limited number of birds in experimental transmission studies. Our quantitative estimates, based on Bayesian methods of inference, reveal that (i) the period of latency of H5N1 influenza virus in unvaccinated chickens is short (mean: 0.24 days; 95% credible interval: 0.099–0.48 days); (ii) the infectious period of H5N1 virus in unvaccinated chickens is approximately 2 days (mean: 2.1 days; 95%CI: 1.8–2.3 days); (iii) the reproduction number of H5N1 virus in unvaccinated chickens need not be high (mean: 1.6; 95%CI: 0.90–2.5), although the virus is expected to spread rapidly because it has a short generation interval in unvaccinated chickens (mean: 1.3 days; 95%CI: 1.0–1.5 days); and (iv) vaccination with genetically and antigenically distant H5N2 vaccines can effectively halt transmission. Simulations based on the estimated parameters indicate that herd immunity may be obtained if at least 80% of chickens in a flock are vaccinated. We discuss the implications for the control of H5N1 avian influenza virus in areas where it is endemic.     

高致病性禽流感与流感病毒

高致病性禽流感最近在东南亚及我国部份地区暴发流行,引致养禽业巨大损失,并危及人类健康.流感病毒继SARS冠状病毒之后,一时成为热点话题.     

Risk Assessment of H2N2 Influenza Viruses from the Avian Reservoir

H2N2 influenza A viruses were the cause of the 1957-1958 pandemic. Historical evidence demonstrates they arose from avian virus ancestors, and while the H2N2 subtype has disappeared from humans, it persists in wild and domestic birds. Reemergence of H2N2 in humans is a significant threat due to the absence of humoral immunity in individuals under the age of 50. Thus, examination of these viruses, particularly those from the avian reservoir, must be addressed through surveillance, characterization, and antiviral testing. The data presented here are a risk assessment of 22 avian H2N2 viruses isolated from wild and domestic birds over 6 decades. Our data show that they have a low rate of genetic and antigenic evolution and remained similar to isolates circulating near the time of the pandemic. Most isolates replicated in mice and human bronchial epithelial cells, but replication in swine tissues was low or absent. Multiple isolates replicated in ferrets, and 3 viruses were transmitted to direct-contact cage mates. Markers of mammalian adaptation in hemagglutinin (HA) and PB2 proteins were absent from all isolates, and they retained a preference for avian-like α2,3-linked sialic acid receptors. Most isolates remained antigenically similar to pandemic A/Singapore/1/57 (H2N2) virus, suggesting they could be controlled by the pandemic vaccine candidate. All viruses were susceptible to neuraminidase inhibitors and adamantanes. Nonetheless, the sustained pathogenicity of avian H2N2 viruses in multiple mammalian models elevates their risk potential for human infections and stresses the need for continual surveillance as a component of prepandemic planning.     

ELISA技术在禽流感诊断研究中的应用

禽流感（AI）是目前禽类流行的主要疫病之一,给养禽业和人类健康带来了巨大危害。由于禽流感病毒血清型众多,致病疫情多样,因此,适时的检测和早期快速诊断是预防和控制禽流感的前提条件。ELISA方法以其特异、灵敏、快速、简便,可迅速检测大量样品,使用仪器设备少,利于基层操作等优点成为AI流行病学普查及早期快速诊断的最实用和有效的方法。     

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.     

Risks of Avian Influenza Transmission in Areas of Intensive Free-Ranging Duck Production with Wild Waterfowl

For decades, southern China has been considered to be an important source for emerging influenza viruses since key hosts live together in high densities in areas with intensive agriculture. However, the underlying conditions of emergence and spread of avian influenza viruses (AIV) have not been studied in detail, particularly the complex spatiotemporal interplay of viral transmission between wild and domestic ducks, two major actors of AIV epidemiology. In this synthesis, we examine the risks of avian influenza spread in Poyang Lake, an area of intensive free-ranging duck production and large numbers of wild waterfowl. Our synthesis shows that farming of free-grazing domestic ducks is intensive in this area and synchronized with wild duck migration. The presence of juvenile domestic ducks in harvested paddy fields prior to the arrival and departure of migrant ducks in the same fields may amplify the risk of AIV circulation and facilitate the transmission between wild and domestic populations. We provide evidence associating wild ducks migration with the spread of H5N1 in the spring of 2008 from southern China to South Korea, Russia, and Japan, supported by documented wild duck movements and phylogenetic analyses of highly pathogenic avian influenza H5N1 sequences. We suggest that prevention measures based on a modification of agricultural practices may be implemented in these areas to reduce the intensity of AIV transmission between wild and domestic ducks. This would require involving all local stakeholders to discuss feasible and acceptable solutions.     

A Multiplex Label-Free Approach to Avian Influenza Surveillance and Serology

Influenza serology has traditionally relied on techniques such as hemagglutination inhibition, microneutralization, and ELISA. These assays are complex, challenging to implement in a format allowing detection of several types of antibody-analyte interactions at once (multiplex), and troublesome to implement in the field. As an alternative, we have developed a hemagglutinin microarray on the Arrayed Imaging Reflectometry (AIR) platform. AIR provides sensitive, rapid, and label-free multiplex detection of targets in complex analyte samples such as serum. In preliminary work, we demonstrated the application of this array to the testing of human samples from a vaccine trial. Here, we report the application of an expanded label-free hemagglutinin microarray to the analysis of avian serum samples. Samples from influenza virus challenge experiments in mallards yielded strong, selective detection of antibodies to the challenge antigen in most cases. Samples acquired in the field from mallards were also analyzed, and compared with viral hemagglutinin inhibition and microneutralization assays. We find that the AIR hemagglutinin microarray can provide a simple and robust alternative to standard methods, offering substantially greater information density from a simple workflow.     

Investigating the Contribution of Peri-domestic Transmission to Risk of Zoonotic Malaria Infection in Humans

BackgroundIn recent years, the primate malaria Plasmodium knowlesi has emerged in human populations throughout South East Asia, with the largest hotspot being in Sabah, Malaysian Borneo. Control efforts are hindered by limited knowledge of where and when people get exposed to mosquito vectors. It is assumed that exposure occurs primarily when people are working in forest areas, but the role of other potential exposure routes (including domestic or peri-domestic transmission) has not been thoroughly investigated.Conclusions/SignificanceThis study shows there is a possibility that humans can be exposed to P. knowlesi infection around their homes. The vector is highly exophagic and few were caught indoors indicating interventions using bednets inside households may have relatively little impact.     

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 Seroprevalence and Biosecurity Risk Factors in Maryland Backyard Poultry: A Cross-Sectional Study

Major implications on a country''s economy, food source, and public health. With recent concern over the highly pathogenic avian influenza outbreaks around the world, government agencies are carefully monitoring and inspecting live bird markets, commercial flocks, and migratory bird populations. However, there remains limited surveillance of non-commercial poultry. Therefore, a cross-sectional study was conducted in backyard poultry flocks using a convenience sampling method across three regions of Maryland from July 2011 to August 2011. The objective of this study was to develop a better understanding of the ecology and epidemiology of avian influenza by investigating the prevalence and seroprevalence in this potentially vulnerable population and by evaluating biosecurity risk factors associated with positive findings. Serum, tracheal, and cloacal swabs were randomly collected from 262 birds among 39 registered premises. Analysis indicated bird and flock seroprevalence as 4.2% (11/262) and 23.1% (9/39), respectively. Based on RT-qPCR analysis, none of the samples were found to be positive for AI RNA and evidence of AI hemagglutinin subtypes H5, H7, or H9 were not detected. Although no statistically significant biosecurity associations were identified (p≤0.05), AI seroprevalence was positively associated with exposure to waterfowl, pest control, and location. AI seropositive flocks exposed to waterfowl were 3.14 times as likely to be AI seropositive than those not exposed (p = 0.15). AI seropositive flocks that did not use pest control were 2.5 times as likely to be AI seropositive compared to those that did and AI seropositive flocks located in the Northern region of Maryland were 2.8 times as likely to be AI seropositive than those that were located elsewhere.     

Aggression and Affiliation during Social Conflict in Pigs

Social conflict is mostly studied in relation to aggression. A more integral approach, including aggressive and affiliative behaviour as well as physiology, may however give a better understanding of the animals'' experience during social conflict. The experience of social conflict may also be reflected in the spatial distribution between conspecifics. The objective was to assess the relationship between behaviour, physiology, and spatial integration in pigs (Sus scrofa) during social conflict. Hereto, 64 groups of pigs (9 wk of age) were studied in a 24 h regrouping test whereby pairs of familiar pigs were grouped with 2 unfamiliar pairs, in either barren or straw-enriched housing. Data on aggressive and affiliative behaviour, skin lesions, body weight, and haptoglobin could be summarized into three principal component analysis factors. These three factors were analysed in relation to spatial integration, i.e. inter-individual distances and lying in body contact. Pigs stayed up to 24 h after encounter in closer proximity to the familiar pig than to unfamiliar pigs. Pigs with a high factor 1 score were more inactive, gave little social nosing, had many skin lesions and a high body weight. They tended to space further away from the familiar pig (b = 1.9 cm; P = 0.08) and unfamiliar ones (b = 0.7 cm; P = 0.05). Pigs that were involved in much aggression (factor 2), and that had a strong increase in haptoglobin (factor 3), tended to be relatively most far away from unfamiliar pigs (b = 0.03 times further; P = 0.08). Results on lying in body contact were coherent with results on distances. Pigs in enriched housing spaced further apart than pigs in barren housing (P<0.001). The combined analysis of measures revealed animals that may either promote or slow down group cohesion, which may not have become clear from single parameters. This emphasizes the importance of an integral approach to social conflict.     

Highly Pathogenic Avian Influenza Virus Infection of Mallards with Homo- and Heterosubtypic Immunity Induced by Low Pathogenic Avian Influenza Viruses

The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 µl at 3 dpi: 3.0×10² vs. 2.3×10⁴ vs. 8.7×10⁴; p<0.05). Heterosubtypic immunity induced by an H4N6 infection mediated a similar but less pronounced effect. We conclude that the epidemiology of HPAIV H5N1 in mallards and probably other aquatic wild bird species is massively influenced by interfering immunity induced by prior homo- and heterosubtypic LPAIV infections.