Improving pandemic influenza risk assessment

Russell, Colin A.; Kasson, Peter M.; Donis, Ruben O.; Riley, Steven; Dunbar, John; Rambaut, Andrew; Asher, Jason; Bürke, S.; Davis, C. Todd; Garten, Rebecca; Gnanakaran, S.; Hay, Simon I.; Herfst, Sander; Lewis, Nicola S.; Lloyd‐Smith, James O.; Macken, Catherine A.; Maurer‐Stroh, Sebastian; Neuhaus, Elizabeth B.; Parrish, Colin R.; Pepin, Kim M.; Shepard, Samuel S.; Smith, David L.; Suarez, David L.; Trock, Susan C.; Widdowson, Marc Alain; George, Dylan B.; Lipsitch, Marc; Bloom, Jesse D.

doi:10.7554/elife.03883

Cited by 61 publications

(63 citation statements)

References 73 publications

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“…Crucially, however, such models consider all emerging diseases in the same manner, regardless of their transmissibility within human populations, even though only a subset will establish endemic transmission. Other studies have considered the "genetic" barriers to emergence in both hosts and viruses (11), particularly the number and origin of the mutations necessary to allow adaptation to human hosts (12), and the challenges of evolving new tissue tropisms (13). Although of fundamental importance, such characteristics are often highly pathogen-specific such that it is difficult to draw generalities about the likelihood of successful emergence.…”

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confidence: 99%

Virological factors that increase the transmissibility of emerging human viruses

Geoghegan

Senior

Giallonardo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

128

133

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The early detection of pathogens with epidemic potential is of major importance to public health. Most emerging infections result in dead-end "spillover" events in which a pathogen is transmitted from an animal reservoir to a human but is unable to achieve the sustained human-to-human transmission necessary for a full-blown epidemic. It is therefore critical to determine why only some virus infections are efficiently transmitted among humans whereas others are not. We sought to determine which biological features best characterized those viruses that have achieved sustained human transmission. Accordingly, we compiled a database of 203 RNA and DNA human viruses and used an information theoretic approach to assess which of a set of key biological variables were the best predictors of human-to-human transmission. The variables analyzed were as follows: taxonomic classification; genome length, type, and segmentation; the presence or absence of an outer envelope; recombination frequency; duration of infection; host mortality; and whether or not a virus exhibits vector-borne transmission. This comparative analysis revealed multiple strong associations. In particular, we determined that viruses with low host mortality, that establish long-term chronic infections, and that are nonsegmented, nonenveloped, and, most importantly, not transmitted by vectors were more likely to be transmissible among humans. In contrast, variables including genome length, genome type, and recombination frequency had little predictive power. In sum, we have identified multiple biological features that seemingly determine the likelihood of interhuman viral transmissibility, in turn enabling general predictions of whether viruses of a particular type will successfully emerge in human populations.virus | evolution | transmission | comparative analysis | spill-over

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confidence: 99%

Virological factors that increase the transmissibility of emerging human viruses

Geoghegan

Senior

Giallonardo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

128

133

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“…So far, sustained spread in humans has been limited to the H1N1, H2N2, and H3N2 subtypes (Kuiken et al, 2006), though it is possible that other subtypes circulated prior to 1918, the year of the first pandemic from which viruses are available for study (Worobey et al, 2014). Multiple virus–host interactions are necessary for replication and onward transmission; the differences in the genetic requirements to accomplish each of these interactions in humans versus other animals provide a barrier to sustained transmission following spillover (Russell et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

“…There are several hurdles to evaluating the accuracy of such predictions (Russell et al, 2014). Factors limiting our ability to identify high-risk viruses and predict the risk they pose include:…”

Section: Introductionmentioning

confidence: 99%

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Viral factors in influenza pandemic risk assessment

Lipsitch

Barclay

Raman

et al. 2016

eLife

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The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk.DOI: http://dx.doi.org/10.7554/eLife.18491.001

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“…As described in more detail throughout this review, results can be influenced by numerous parameters, including, but not limited to, stock generation and passage history, the age, gender, and immunological background of the ferrets used, the housing and environmental conditions under which the experiment is performed, the route and dose of virus inoculation, the timing and choice of sample collection, and the design of the transmission setup. As there is an ongoing need to improve the basis for assessment of the risks posed by influenza viruses (9), understanding the role that these choices in experimental design can play in research studies and how these mammalian models can be further improved for use in risk assessment is critical.…”

Section: Introductionmentioning

confidence: 99%

Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models

Belser

Eckert

Tumpey

et al. 2016

Microbiol Mol Biol Rev

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SUMMARYFerrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses.

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Improving pandemic influenza risk assessment

Cited by 61 publications

References 73 publications

Virological factors that increase the transmissibility of emerging human viruses

Virological factors that increase the transmissibility of emerging human viruses

Viral factors in influenza pandemic risk assessment

Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models

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