scholarly journals Virulence attenuation during an influenza A/H5N1 pandemic

2013 ◽  
Vol 368 (1614) ◽  
pp. 20120207 ◽  
Author(s):  
Maciej F. Boni ◽  
Tran Dang Nguyen ◽  
Menno D. de Jong ◽  
H. Rogier van Doorn
Keyword(s):  
Influenza A ◽  
Evolutionary Dynamics ◽  
Deterministic Model ◽  
Case Fatality ◽  
Social Distancing ◽  
Virulence Evolution ◽  
Virulence Attenuation ◽  
Evolutionary Features ◽  
Individual Based Simulation ◽  
Human H5n1

More than 15 years after the first human cases of influenza A/H5N1 in Hong Kong, the world remains at risk for an H5N1 pandemic. Preparedness activities have focused on antiviral stockpiling and distribution, development of a human H5N1 vaccine, operationalizing screening and social distancing policies, and other non-pharmaceutical interventions. The planning of these interventions has been done in an attempt to lessen the cumulative mortality resulting from a hypothetical H5N1 pandemic. In this theoretical study, we consider the natural limitations on an H5N1 pandemic's mortality imposed by the virus' epidemiological–evolutionary constraints. Evolutionary theory dictates that pathogens should evolve to be relatively benign, depending on the magnitude of the correlation between a pathogen's virulence and its transmissibility. Because the case fatality of H5N1 infections in humans is currently 60 per cent, it is doubtful that the current viruses are close to their evolutionary optimum for transmission among humans. To describe the dynamics of virulence evolution during an H5N1 pandemic, we build a mathematical model based on the patterns of clinical progression in past H5N1 cases. Using both a deterministic model and a stochastic individual-based simulation, we describe (i) the drivers of evolutionary dynamics during an H5N1 pandemic, (ii) the range of case fatalities for which H5N1 viruses can successfully cause outbreaks in humans, and (iii) the effects of different kinds of social distancing on virulence evolution. We discuss two main epidemiological–evolutionary features of this system (i) the delaying or slowing of an epidemic which results in a majority of hosts experiencing an attenuated virulence phenotype and (ii) the strong evolutionary pressure for lower virulence experienced by the virus during a period of intense social distancing.

scholarly journals Age-specific infection and death rates for human A(H5N1) avian influenza in Egypt

2009 ◽  
Vol 14 (18) ◽  
Author(s):  
J P Dudley
Keyword(s):  
Influenza A ◽  
Case Fatality Rate ◽  
Case Fatality ◽  
Age Group ◽  
Fatality Rate ◽  
Death Rates ◽  
H5n1 Avian Influenza ◽  
Human H5n1 ◽  
Sex Biases ◽  
Age And Sex

The age-specific infection and death profiles among confirmed human cases of influenza A(H5N1) infection in Egypt differ markedly from those recorded in other countries. The case fatality rate among human H5N1 cases in Egypt is 34%, versus an average of 66% in other countries. In Egypt, children younger than 10 years comprise 48% of reported cases, nearly twice the global average of approximately 25%, and no H5N1 fatalities have been confirmed among individuals in this age group as of 23 April 2009. Females outnumber males among confirmed H5N1 cases by a factor of nearly 2:1, and 90% of reported fatalities in Egypt have been females. The evident age and sex biases in morbidity and mortality among H5N1 cases in Egypt are phenomena that warrant further investigation and analysis.

scholarly journals Evolutionary features of a prolific subtype of avian influenza A virus in European waterfowl

2021 ◽  
Author(s):  
Michelle Wille ◽  
Conny Tolf ◽  
Neus Latorre-Margalef ◽  
Ron A. M. Fouchier ◽  
Rebecca A. Halpin ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A Virus ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Phylogenetic Analyses ◽  
Reservoir Host ◽  
Amino Acid Sequences ◽  
Evolutionary Features ◽  
Avian Influenza A Virus ◽  
Genetic Features

Avian influenza A virus (AIV) is ubiquitous in waterfowl, and detected annually at high prevalence in waterfowl during the Northern Hemipshere autumn. Some AIV subtypes are globally common in waterfowl, such as H3N8, H4N6, and H6N2, and are detected in the same populations at high frequency, annually. In order to investigate genetic features associated to the long-term maintenance of common subtypes in migratory ducks, we sequenced 248 H4 viruses isolated across 8 years (2002-2009) from Mallards (Anas platyrhynchos) sampled in southeast Sweden. Phylogenetic analyses showed that both H4 and N6 sequences fell into in three distinct lineages, structured by year of isolation. Specifically, across the eight years of the study, we observed lineage replacement, whereby a different HA lineage circulated in the population each year. Analysis of deduced amino acid sequences of the HA lineages illustrated key differences in regions of the globular head of hemagglutinin that overlap with established antigentic sites in homologous hemagglutinin H3, suggesting the possibility of antigenic differences among these HA lineages. Beyond HA, lineage replacement was common to all segments, such that novel genome constellations were detected across years. A dominant genome constellation would rapidly amplify in the duck population, followed by unlinking of gene segments as a result of reassortment within 2-3 weeks following introduction. These data help reveal the evolutionary dynamics exhibited by AIV on both annual and decadal scales in an important reservoir host.

scholarly journals The Effects of Social Distancing Policies on non-SARS-CoV-2 Respiratory Pathogens

2021 ◽  
Author(s):  
Jeff Nawrocki ◽  
Katherine Olin ◽  
Martin C Holdrege ◽  
Joel Hartsell ◽  
Lindsay Meyers ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Detection Rate ◽  
Respiratory Illness ◽  
Respiratory Pathogens ◽  
Public Health Response ◽  
Mixed Effect ◽  
Detection Rates ◽  
Social Distancing ◽  
The Impact

Abstract Background The initial focus of the US public health response to COVID-19 was the implementation of numerous social distancing policies. While COVID-19 was the impetus for imposing these policies, it is not the only respiratory disease affected by their implementation. This study aimed to assess the impact of social distancing policies on non-SARS-CoV-2 respiratory pathogens typically circulating across multiple US states. Methods Linear mixed-effect models were implemented to explore the effects of five social distancing policies on non-SARS-CoV-2 respiratory pathogens across nine states from January 1 through May 1, 2020. The observed 2020 pathogen detection rates were compared week-by-week to historical rates to determine when the detection rates were different. Results Model results indicate that several social distancing policies were associated with a reduction in total detection rate, by nearly 15%. Policies were associated with decreases in pathogen circulation of human rhinovirus/enterovirus and human metapneumovirus, as well as influenza A, which typically decrease after winter. Parainfluenza viruses failed to circulate at historical levels during the spring. Total detection rate in April 2020 was 35% less than historical average. Many of the pathogens driving this difference fell below historical detection rate ranges within two weeks of initial policy implementation. Conclusion This analysis investigated the effect of multiple social distancing policies implemented to reduce transmission of SARS-CoV-2 on non-SARS-CoV-2 respiratory pathogens. These findings suggest that social distancing policies may be used as an impactful public health tool to reduce communicable respiratory illness.

scholarly journals Population Diversity and Collective Interactions during Influenza Virus Infection

2017 ◽  
Vol 91 (22) ◽  
Author(s):  
Christopher B. Brooke
Keyword(s):  
Genome Organization ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Influenza Virus Infection ◽  
Population Diversity ◽  
Genomic Diversity ◽  
Global Public Health ◽  
Public Health Threat ◽  
Genetic Makeup ◽  
Collective Interactions

ABSTRACT Influenza A virus (IAV) continues to pose an enormous and unpredictable global public health threat, largely due to the continual evolution of escape from preexisting immunity and the potential for zoonotic emergence. Understanding how the unique genetic makeup and structure of IAV populations influences their transmission and evolution is essential for developing more-effective vaccines, therapeutics, and surveillance capabilities. Owing to their mutation-prone replicase and unique genome organization, IAV populations exhibit enormous amounts of diversity both in terms of sequence and functional gene content. Here, I review what is currently known about the genetic and genomic diversity present within IAV populations and how this diversity may shape the replicative and evolutionary dynamics of these viruses.

scholarly journals The Dynamics of Influenza A H3N2 Defective Viral Genomes from a Human Challenge Study

2019 ◽  
Author(s):  
Michael A. Martin ◽  
Drishti Kaul ◽  
Gene S. Tan ◽  
Christopher W. Woods ◽  
Katia Koelle
Keyword(s):  
Genetic Drift ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Gene Segment ◽  
Influenza Viruses ◽  
Genomic Variation ◽  
Wild Type Virus ◽  
Single Nucleotide Variants ◽  
Viral Genomes

AbstractThe rapid evolution of influenza is an important contributing factor to its high worldwide incidence. The emergence and spread of genetic point mutations has been thoroughly studied both within populations and within individual hosts. In addition, influenza viruses are also known to generate genomic variation during their replication in the form of defective viral genomes (DVGs). These DVGs are formed by internal deletions in at least one gene segment that render them incapable of replication without the presence of wild-type virus. DVGs have previously been identified in natural human infections and may be associated with less severe clinical outcomes. These studies have not been able to address how DVG populations evolve in vivo in individual infections due to their cross-sectional design. Here we present an analysis of DVGs present in samples from two longitudinal influenza A H3N2 human challenge studies. We observe the generation of DVGs in almost all subjects. Although the genetic composition of DVG populations was highly variable, identical DVGs were observed both between multiple samples within single hosts as well as between hosts. Most likely due to stochastic effects, we did not observe clear instances of selection for specific DVGs or for shorter DVGs over the course of infection. Furthermore, DVG presence was not found to be associated with peak viral titer or peak symptom scores. Our analyses highlight the diversity of DVG populations within a host over the course of infection and the apparent role that genetic drift plays in their population dynamics.ImportanceThe evolution of influenza virus, in terms of single nucleotide variants and the reassortment of gene segments, has been studied in detail. However, influenza is known to generate defective viral genomes (DVGs) during replication, and little is known about how these genomes evolve both within hosts and at the population level. Studies in animal models have indicated that prophylactically or therapeutically administered DVGs can impact patterns of disease progression. However, the formation of naturally-occurring DVGs, their evolutionary dynamics, and their contribution to disease severity in human hosts is not well understood. Here, we identify the formation of de novo DVGs in samples from human challenge studies throughout the course of infection. We analyze their evolutionary trajectories, revealing the important role of genetic drift in shaping DVG populations during acute infections with well-adapted viral strains.

scholarly journals An Avian H7N1 Gain-of-Function Experiment of Great Concern

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Simon Wain-Hobson
Keyword(s):  
Influenza A ◽  
Case Fatality ◽  
Influenza A Viruses ◽  
Gain Of Function ◽  
Highly Pathogenic ◽  
Dead End ◽  
Spanish Flu ◽  
Potential Risks ◽  
Novel Virus ◽  
H7n1 Virus

ABSTRACT Inappropriately named gain-of-function influenza research seeks to confer airborne transmission on avian influenza A viruses that otherwise cause only dead-end infections in humans. A recent study has succeeded in doing this with a highly pathogenic ostrich H7N1 virus in a ferret model without loss of virulence. If transposable to humans, this would constitute a novel virus with a case fatality rate ~30 greater than that of Spanish flu. A commentary from three distinguished virologists considered the benefits of this work to outweigh potential risks. I beg to disagree with conclusions in both papers, for the underlying science is not as strong as it appears.

scholarly journals Evolutionary Dynamics and Global Diversity of Influenza A Virus

2015 ◽  
Vol 89 (21) ◽  
pp. 10993-11001 ◽  
Author(s):  
Daniel Rejmanek ◽  
Parviez R. Hosseini ◽  
Jonna A. K. Mazet ◽  
Peter Daszak ◽  
Tracey Goldstein
Keyword(s):  
East Asia ◽  
Influenza A Virus ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Nucleotide Substitution ◽  
Health Care Spending ◽  
Asian Countries ◽  
Substitution Rates ◽  
Country Level ◽  
Nucleotide Substitution Rates

ABSTRACTThe increasing number of zoonotic infections caused by influenza A virus (IAV) subtypes of avian origin (e.g., H5N1 and H7N9) in recent years underscores the need to better understand the factors driving IAV evolution and diversity. To evaluate the current feasibility of global analyses to contribute to this aim, we evaluated information in the public domain to explore IAV evolutionary dynamics, including nucleotide substitution rates and selection pressures, using 14 IAV subtypes in 32 different countries over a 12-year period (2000 to 2011). Using geospatial information from 39,785 IAV strains, we examined associations between subtype diversity and socioeconomic, biodiversity, and agricultural indices. Our analyses showed that nucleotide substitution rates for 11 of the 14 evaluated subtypes tended to be higher in Asian countries, particularly in East Asia, than in Canada and the United States. Similarly, at a regional level, subtypes H5N1, H5N2, and H6N2 exhibited significantly higher substitution rates in East Asia than in North America. In contrast, the selection pressures (measured as ratios of nonsynonymous to synonymous evolutionary changes [dN/dSratios]) acting on individual subtypes showed little geographic variation. We found that the strongest predictors for the detected subtype diversity at the country level were reporting effort (i.e., total number of strains reported) and health care spending (an indicator of economic development). Our analyses also identified major global gaps in IAV reporting (including a lack of sequences submitted from large portions of Africa and South America and a lack of geolocation information) and in broad subtype testing which, until addressed, will continue to hinder efforts to track the evolution and diversity of IAV around the world.IMPORTANCEIn recent years, an increasing number of influenza A virus (IAV) subtypes, including H5N1, H7N9, and H10N8, have been detected in humans. High fatality rates have led to an increased urgency to better understand where and how novel pathogenic influenza virus strains emerge. Our findings showed that mutational rates of 11 commonly encountered subtypes were higher in East Asian countries than in North America, suggesting that there may be a greater risk for the emergence of novel pathogenic strains in East Asia. In assessing the potential drivers of IAV subtype diversity, our analyses confirmed that reporting effort and health care spending were the best predictors of the observed subtype diversity at the country level. These findings underscore the need to increase sampling and reporting efforts for all subtypes in many undersampled countries throughout the world.

scholarly journals Transient virulence of emerging pathogens

2009 ◽  
Vol 7 (46) ◽  
pp. 811-822 ◽  
Author(s):  
Benjamin M. Bolker ◽  
Arjun Nanda ◽  
Dharmini Shah
Keyword(s):  
Genetic Variance ◽  
Evolutionary Dynamics ◽  
Growth Conditions ◽  
Emerging Pathogens ◽  
Potential Significance ◽  
Phase Selection ◽  
Transmission Rates ◽  
Virulence Evolution ◽  
High Virulence ◽  
Highly Virulent

Should emerging pathogens be unusually virulent? If so, why? Existing theories of virulence evolution based on a tradeoff between high transmission rates and long infectious periods imply that epidemic growth conditions will select for higher virulence, possibly leading to a transient peak in virulence near the beginning of an epidemic. This transient selection could lead to high virulence in emerging pathogens. Using a simple model of the epidemiological and evolutionary dynamics of emerging pathogens, along with rough estimates of parameters for pathogens such as severe acute respiratory syndrome, West Nile virus and myxomatosis, we estimated the potential magnitude and timing of such transient virulence peaks. Pathogens that are moderately evolvable, highly transmissible, and highly virulent at equilibrium could briefly double their virulence during an epidemic; thus, epidemic-phase selection could contribute significantly to the virulence of emerging pathogens. In order to further assess the potential significance of this mechanism, we bring together data from the literature for the shapes of tradeoff curves for several pathogens (myxomatosis, HIV, and a parasite of Daphnia ) and the level of genetic variation for virulence for one (myxomatosis). We discuss the need for better data on tradeoff curves and genetic variance in order to evaluate the plausibility of various scenarios of virulence evolution.

scholarly journals The evolutionary dynamics of influenza A virus adaptation to mammalian hosts

2013 ◽  
Vol 368 (1614) ◽  
pp. 20120382 ◽  
Author(s):  
S. Bhatt ◽  
T. T. Lam ◽  
S. J. Lycett ◽  
A. J. Leigh Brown ◽  
T. A. Bowden ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Adaptive Evolution ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Adaptive Dynamics ◽  
Swine Influenza ◽  
Influenza Viruses ◽  
Viral Fitness ◽  
Influenza A Viruses ◽  
Entire Genome

Few questions on infectious disease are more important than understanding how and why avian influenza A viruses successfully emerge in mammalian populations, yet little is known about the rate and nature of the virus’ genetic adaptation in new hosts. Here, we measure, for the first time, the genomic rate of adaptive evolution of swine influenza viruses (SwIV) that originated in birds. By using a curated dataset of more than 24 000 human and swine influenza gene sequences, including 41 newly characterized genomes, we reconstructed the adaptive dynamics of three major SwIV lineages (Eurasian, EA; classical swine, CS; triple reassortant, TR). We found that, following the transfer of the EA lineage from birds to swine in the late 1970s, EA virus genes have undergone substantially faster adaptive evolution than those of the CS lineage, which had circulated among swine for decades. Further, the adaptation rates of the EA lineage antigenic haemagglutinin and neuraminidase genes were unexpectedly high and similar to those observed in human influenza A. We show that the successful establishment of avian influenza viruses in swine is associated with raised adaptive evolution across the entire genome for many years after zoonosis, reflecting the contribution of multiple mutations to the coordinated optimization of viral fitness in a new environment. This dynamics is replicated independently in the polymerase genes of the TR lineage, which established in swine following separate transmission from non-swine hosts.

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