scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Genetic Data Provide Evidence for Wind-Mediated Transmission of Highly Pathogenic Avian Influenza

TL;DR: Using detailed genetic and epidemiological data, statistical evidence is provided that the direction of spread of avian influenza A(H7N7) is correlated with thedirection of wind at date of infection.
Abstract: Outbreaks of highly pathogenic avian influenza in poultry can cause severe economic damage and represent a public health threat. Development of efficient containment measures requires an understanding of how these influenza viruses are transmitted between farms. However, the actual mechanisms of interfarm transmission are largely unknown. Dispersal of infectious material by wind has been suggested, but never demonstrated, as a possible cause of transmission between farms. Here we provide statistical evidence that the direction of spread of avian influenza A(H7N7) is correlated with the direction of wind at date of infection. Using detailed genetic and epidemiological data, we found the direction of spread by reconstructing the transmission tree for a large outbreak in the Netherlands in 2003. We conservatively estimate the contribution of a possible wind-mediated mechanism to the total amount of spread during this outbreak to be around 18%.

Content maybe subject to copyright    Report

Citations
More filters
Journal ArticleDOI
01 Nov 2013-Genetics
TL;DR: The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology by simultaneously estimating the phylogenetic tree and the transmission tree.
Abstract: Transmission events are the fundamental building blocks of the dynamics of any infectious disease. Much about the epidemiology of a disease can be learned when these individual transmission events are known or can be estimated. Such estimations are difficult and generally feasible only when detailed epidemiological data are available. The genealogy estimated from genetic sequences of sampled pathogens is another rich source of information on transmission history. Optimal inference of transmission events calls for the combination of genetic data and epidemiological data into one joint analysis. A key difficulty is that the transmission tree, which describes the transmission events between infected hosts, differs from the phylogenetic tree, which describes the ancestral relationships between pathogens sampled from these hosts. The trees differ both in timing of the internal nodes and in topology. These differences become more pronounced when a higher fraction of infected hosts is sampled. We show how the phylogenetic tree of sampled pathogens is related to the transmission tree of an outbreak of an infectious disease, by the within-host dynamics of pathogens. We provide a statistical framework to infer key epidemiological and mutational parameters by simultaneously estimating the phylogenetic tree and the transmission tree. We test the approach using simulations and illustrate its use on an outbreak of foot-and-mouth disease. The approach unifies existing methods in the emerging field of phylodynamics with transmission tree reconstruction methods that are used in infectious disease epidemiology.

166 citations


Cites background from "Genetic Data Provide Evidence for W..."

  • ...More importantly, transmission tree reconstruction allows for an understanding of the outbreak at a high level of detail; for example, hypotheses regarding the transmission mechanism can be tested using the reconstructed transmission tree (Ypma et al. 2013)....

    [...]

  • ...…2001; Keeling et al. 2003; Wallinga and Teunis 2004; Heijne et al. 2009), to quantify superspreading (Lloyd-Smith et al. 2005), to estimate key parameters (Haydon et al. 2003; Heijne et al. 2012; Hens et al. 2012), and to identify mechanisms of transmission (Spada et al. 2004; Ypma et al. 2013)....

    [...]

Journal ArticleDOI
TL;DR: Whether the widespread use of the H5N1 vaccine in east Asia—with suboptimum biosecurity measures in live poultry markets and farms—predisposed to the emergence of H7N9 or other virus subtypes needs further investigation.
Abstract: Summary Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9 virus in 2013 caused severe pneumonia that did not respond to typical or atypical antimicrobial treatment, and resulted in high mortality. Both viruses are reassortants with internal genes derived from avian influenza A H9N2 viruses that circulate in Asian poultry. Both viruses have genetic markers of mammalian adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced binding to human-type receptors and improved replication in mammals, respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9 in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing in human population and poultry consumption before the outbreaks. Both cities are located along the avian migratory route at the Pearl River delta and Yangtze River delta. Whether the widespread use of the H5N1 vaccine in east Asia—with suboptimum biosecurity measures in live poultry markets and farms—predisposed to the emergence of H7N9 or other virus subtypes needs further investigation. Why H7N9 seems to be more readily transmitted from poultry to people than H5N1 is still unclear.

137 citations

Journal ArticleDOI
TL;DR: Seasonality of influenza is largely dictated by temperature and humidity, with cool-dry conditions enhancing IAV survival and transmissibility in temperate climates in high latitudes, whereas humid-rainy conditions favor outbreaks in low latitude, as seen in tropical and subtropical zones.
Abstract: The environmental drivers of influenza outbreaks are largely unknown. Despite more than 50 years of research, there are conflicting lines of evidence on the role of the environment in influenza A virus (IAV) survival, stability, and transmissibility. With the increasing and looming threat of pandemic influenza, it is important to understand these factors for early intervention and long-term control strategies. The factors that dictate the severity and spread of influenza would include the virus, natural and acquired hosts, virus-host interactions, environmental persistence, virus stability and transmissibility, and anthropogenic interventions. Virus persistence in different environments is subject to minor variations in temperature, humidity, pH, salinity, air pollution, and solar radiations. Seasonality of influenza is largely dictated by temperature and humidity, with cool-dry conditions enhancing IAV survival and transmissibility in temperate climates in high latitudes, whereas humid-rainy conditions f...

101 citations

Journal ArticleDOI
TL;DR: This work has developed a novel approach to reconstruct transmission trees with sequence data that combines elementary models for transmission, case observation, within-host pathogen dynamics, and mutation, under the assumption that the outbreak is over and all cases have been observed.
Abstract: Whole-genome sequencing of pathogens from host samples becomes more and more routine during infectious disease outbreaks. These data provide information on possible transmission events which can be used for further epidemiologic analyses, such as identification of risk factors for infectivity and transmission. However, the relationship between transmission events and sequence data is obscured by uncertainty arising from four largely unobserved processes: transmission, case observation, within-host pathogen dynamics and mutation. To properly resolve transmission events, these processes need to be taken into account. Recent years have seen much progress in theory and method development, but existing applications make simplifying assumptions that often break up the dependency between the four processes, or are tailored to specific datasets with matching model assumptions and code. To obtain a method with wider applicability, we have developed a novel approach to reconstruct transmission trees with sequence data. Our approach combines elementary models for transmission, case observation, within-host pathogen dynamics, and mutation, under the assumption that the outbreak is over and all cases have been observed. We use Bayesian inference with MCMC for which we have designed novel proposal steps to efficiently traverse the posterior distribution, taking account of all unobserved processes at once. This allows for efficient sampling of transmission trees from the posterior distribution, and robust estimation of consensus transmission trees. We implemented the proposed method in a new R package phybreak. The method performs well in tests of both new and published simulated data. We apply the model to five datasets on densely sampled infectious disease outbreaks, covering a wide range of epidemiological settings. Using only sampling times and sequences as data, our analyses confirmed the original results or improved on them: the more realistic infection times place more confidence in the inferred transmission trees.

96 citations


Cites background or methods from "Genetic Data Provide Evidence for W..."

  • ...Sampling of infection times and infectors could be constrained by these additional data (as in [12, 30]) and could then become less dependent on the sampling times and sampling interval distribution, as in the current implementation....

    [...]

  • ...Another example is the use of spatial data in combination with a spatial transmission kernel, so that the likelihood of infectors includes a distance-dependency, a possible extension motivated by the FMD and H7N7 analyses (as in [9, 30])....

    [...]

  • ...Using geographic data as in earlier analyses [12, 30] will probably place these cases within that cluster....

    [...]

  • ...Consensus Edmonds’ transmission tree for the H7N7 dataset [12, 28, 30]....

    [...]

Journal ArticleDOI
TL;DR: A statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information is described, enabling reconstruction of partially observed transmission trees and estimating the number of cases missing from the sample.
Abstract: We describe a statistical framework for reconstructing the sequence of transmission events between observed cases of an endemic infectious disease using genetic, temporal and spatial information. Previous approaches to reconstructing transmission trees have assumed all infections in the study area originated from a single introduction and that a large fraction of cases were observed. There are as yet no approaches appropriate for endemic situations in which a disease is already well established in a host population and in which there may be multiple origins of infection, or that can enumerate unobserved infections missing from the sample. Our proposed framework addresses these shortcomings, enabling reconstruction of partially observed transmission trees and estimating the number of cases missing from the sample. Analyses of simulated datasets show the method to be accurate in identifying direct transmissions, while introductions and transmissions via one or more unsampled intermediate cases could be identified at high to moderate levels of case detection. When applied to partial genome sequences of rabies virus sampled from an endemic region of South Africa, our method reveals several distinct transmission cycles with little contact between them, and direct transmission over long distances suggesting significant anthropogenic influence in the movement of infected dogs.

86 citations


Cites background from "Genetic Data Provide Evidence for W..."

  • ...This approach enables inferences to be made about epidemiological processes [6], the transmission tree [6,7], the mechanism of transmission [8] and the rate of evolution ‘per transmission event’ [9]....

    [...]

References
More filters
Journal ArticleDOI
TL;DR: Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.
Abstract: Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.

1,039 citations


"Genetic Data Provide Evidence for W..." refers background in this paper

  • ...In this outbreak, 241 poultry farms were infected (confirmed by virus isolation), 30 million birds were culled, and there was 1 human fatality [16, 17]....

    [...]

Journal ArticleDOI
TL;DR: Reconstruction of the genes of the 1918 pandemic virus and studies on their contribution to virulence will be important steps toward understanding the biological capabilities of this lethal virus.
Abstract: Influenza remains an important disease in humans and animals. In contrast to measles, smallpox and poliomyelitis, influenza is caused by viruses that undergo continuous antigenic change and that possess an animal reservoir. Thus, new epidemics and pandemics are likely to occur in the future, and eradication of the disease will be difficult to achieve. Although it is not clear whether a new pandemic is imminent, it would be prudent to take into account the lessons we have learned from studying different human and animal influenza viruses. Specifically, reconstruction of the genes of the 1918 pandemic virus and studies on their contribution to virulence will be important steps toward understanding the biological capabilities of this lethal virus. Increasing the availability of new antiviral drugs and developing superior vaccines will provide us with better approaches to control influenza and to have a positive impact on disease load. A concern is that the imposition of new rules for working with infectious influenza viruses under high security and high containment conditions will stifle scientific progress. The complex questions of what makes an influenza virus transmissible from one human to another and from one species to another, as well as how the immune system interacts with the virus, will require the active collaboration and unencumbered work of many scientific groups.

570 citations

Journal ArticleDOI
TL;DR: In this article, a field survey of dust concentrations within and dust emissions from cattle, pig and poultry buildings was conducted in England, the Netherlands, Denmark and Germany, where measurements of inhalable and respirable dust concentrations were made in 329 buildings and CO 2 within and outside the buildings were also measured to estimate ventilation rates for dust emission calculations.

354 citations


"Genetic Data Provide Evidence for W..." refers background in this paper

  • ...Poultry farms emit large quantities of particulate matter [8, 9], which could be driven by wind to transport viable virus from an infected farm to an uninfected farm [10]....

    [...]

Journal ArticleDOI
TL;DR: Sequence analysis of all eight genes of the LPAI virus and the HPAI viruses showed minor differences between the viruses except at the hemagglutinin (HA) cleavage site, which indicates a virulence shift.
Abstract: Influenza A viruses occur worldwide in wild birds and are occasionally associated with outbreaks in commercial chickens and turkeys. However, avian influenza viruses have not been isolated from wild birds or poultry in South America. A recent outbreak in chickens of H7N3 low pathogenic avian influenza (LPAI) occurred in Chile. One month later, after a sudden increase in deaths, H7N3 highly pathogenic avian influenza (HPAI) virus was isolated. Sequence analysis of all eight genes of the LPAI virus and the HPAI viruses showed minor differences between the viruses except at the hemagglutinin (HA) cleavage site. The LPAI virus had a cleavage site similar to other low pathogenic H7 viruses, but the HPAI isolates had a 30 nucleotide insert. The insertion likely occurred by recombination between the HA and nucleoprotein genes of the LPAI virus, resulting in a virulence shift. Sequence comparison of all eight gene segments showed the Chilean viruses were also distinct from all other avian influenza viruses and represent a distinct South American clade.

327 citations

Journal ArticleDOI
TL;DR: Improved knowledge on particle morphology, primarily size, composition, levels, and the factors influencing these can be useful to identify and quantify sources of PM more accurately, to evaluate their effects, and to propose adequate abatement strategies in livestock houses.

313 citations


"Genetic Data Provide Evidence for W..." refers background in this paper

  • ...Several techniques, such as air scrubbers, water or oil sprinkling, changes in ventilation rate, and ionization systems, have been shown to reduce dust concentrations [8, 24] and could be...

    [...]

  • ...Poultry farms emit large quantities of particulate matter [8, 9], which could be driven by wind to transport viable virus from an infected farm to an uninfected farm [10]....

    [...]

  • ...particulate matter [8], which could carry viable virus [13]....

    [...]