Mapping influenza transmission in the ferret model to transmission in humans
- University of California, Los Angeles, United States
- National Institutes of Health, United States
- Centers for Disease Control and Prevention, United States
Figures
Figure 1 with 1 supplement
Boxplots of influenza SAR estimates by subtype.
(A) Human SAR, (B) ferret respiratory droplet SAR, and (C) ferret direct contact SAR. Solid, black lines represent the subtype medians. Boxes give the inter-quartile range with whiskers extending …
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Figure 1—source data 1
Estimates of human household SAR.
- https://doi.org/10.7554/eLife.07969.004
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Figure 1—source data 2
Ferret influenza transmission studies via respiratory droplets using human isolates.
- https://doi.org/10.7554/eLife.07969.005
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Figure 1—source data 3
Ferret influenza transmission studies via direct contact using human isolates.
- https://doi.org/10.7554/eLife.07969.006
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Figure 1—source data 4
Ferret influenza transmission studies via respiratory droplets and direct contact using avian isolates.
- https://doi.org/10.7554/eLife.07969.007
Figure 1—figure supplement 1
Analysis supporting inclusion of SAR estimates from isolates generating using reverse genetics.
Comparison of ferret SAR for wild-type influenza isolates and their counterparts engineered using reverse genetics under (A) respiratory droplet and (B) direct contact transmission. Because …
Figure 2 with 1 supplement
Analysis of subtype-specific SAR.
(A) Comparison of human SAR and ferret SAR for ferret respiratory droplet (black squares) and direct contact (red circles). Data points are the mean human SAR by subtype vs the weighted mean ferret …
Figure 2—figure supplement 1
Analysis of subtype-specific SAR including avian isolates for H5N1 and H7N9.
(A) Comparison of human SAR and ferret SAR for ferret respiratory droplet (black squares) and direct contact (red circles). Lines give the best fit weighted linear regression models with weights …
Figure 3 with 3 supplements
Weighted logistic regression predicting the probability of a supercritical classification based on ferret SAR.
(A) Respiratory droplet SAR and (B) direct contact SAR. Solid black line gives the fit of the weighted logistic regression, where model weights are given by the number of ferrets in each experiment. …
Figure 3—figure supplement 1
Comparison of ferret SAR via respiratory droplet and direct contact transmission for single influenza isolates.
Each point represents a single set of experiments that tested an isolate for transmission in ferrets under both respiratory droplet and direct contact transmission with other experimental protocols …
Figure 3—figure supplement 2
Effect of uncertainty in ferret SAR on its relationship with the probability of being classified as supercritical.
(A) Respiratory droplet SAR and (B) direct contact SAR. To assess the impact of binomial uncertainty in ferret SAR estimates, we simulated 1000 datasets by taking binomial samples from each data …
Figure 3—figure supplement 3
ROC curves for classifying pandemic potential using different definitions of transmission and transmission routes.
Receiver operating characteristic (ROC) curves and area under the curve (AUC) using (A) seroconversion and/or viral isolation or (B) viral isolation alone as evidence for transmission in ferrets …
Figure 4 with 1 supplement
Predictions of the transmission pattern for current and historical isolates of concern.
(A) Gain-of-function experiments with H5N1 avian influenza (Herfst et al., 2012; Imai et al., 2012), (B) the reconstructed 1918 pandemic H1N1 strain (Tumpey et al., 2007; Imai et al., 2012), and (C) …
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Figure 4—source data 1
Ferret influenza transmission studies via respiratory droplets using strains from gain-of-function experiments with H5N1 avian influenza and the reconstructed 1918 pandemic H1N1 strain.
- https://doi.org/10.7554/eLife.07969.017
Figure 4—figure supplement 1
Sample size calculations.
Sample size estimates to achieve 80% power at a significance level of 0.05 when testing whether a ferret SAR estimate is greater than the lower limit of the identified supercritical window (0.643, Fi…
Tables
Table 1
Parameter estimates for the weighted logistic regression relating human transmission class to ferret SAR
| Data | Model | β0 | βRD | βDC | ΔAIC |
|---|---|---|---|---|---|
| Full data | Direct contact | −4.39 | - | 6.30 | - |
| Respiratory droplet | −3.52 | 6.10 | - | - | |
| Restricted data | Respiratory droplet + direct contact | −1.76 | 8.72 | −3.76 | 0 |
| Respiratory droplet | −3.77 | 6.42 | - | 3.623 | |
| Direct contact | −3.07 | - | 3.74 | 57.348 |
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Bolded estimates are significant at the α = 0.05 level. Due to differing data between ferret respiratory droplet and direct contact transmission experiments, no model selection was done on the full data. Instead, model selection was done only for studies where authors performed respiratory droplet and direct contact transmission experiments on the same isolate.
