DOI: 10.5061/dryad.51c59zw4v
title: Virulence-mediated infectiousness and activity trade-offs and their impact on transmission potential of patients infected with influenza

description: Communicable diseases are often virulent, i.e., they cause morbidity
 symptoms in those infected. While some symptoms may be
 transmission-enhancing, other symptoms are likely to reduce transmission
 potential. For human diseases, the reduction in transmission opportunities
 is commonly caused by reduced activity. There is limited data regarding
 the potential impact of virulence on transmission potential. We performed
 an exploratory data analysis of 324 influenza patients at a university
 health center during the 2016/2017 influenza season. We classified
 symptoms as infectiousness-related or morbidity-related and calculated two
 scores. The scores were used to explore the relationship between
 infectiousness, morbidity (virulence), and activity level. We found a
 decrease in activity level with increasing morbidity scores. There was no
 consistent pattern between activity level and infectiousness score. We
 also found a positive correlation between morbidity and infectiousness
 scores. Overall, we find that increasing virulence leads to increased
 infectiousness and reduced activity, suggesting a trade-off that can
 impact overall transmission potential. Our findings indicate that a
 reduction of systemic symptoms may increase host activity without reducing
 infectiousness. Therefore, interventions should target both systemic and
 infectiousness related symptoms to reduce overall transmission potential.
 Our findings can also inform simulation models that investigate the impact
 of different interventions on transmission.
description: Students with a
 primary complaint related to a respiratory infection who made an
 appointment at the health center of a large research university from
 December 2016 to February 2017 filled out an electronic questionnaire. The
 questionnaire collected data about their current symptoms and activity
 level. A response was required for all symptom-related questions when they
 scheduled their appointments. We included all symptoms collected by the
 questionnaire in this analysis. The complete questionnaire is
 available.
description: <strong>Description of Included Files</strong> “<b>Virulence_Trade-off.Rproj</b>” This file lets R know the relative file paths for loading and saving files. “<b>SymptomActivity.bib</b>” This file has all of the citation saved as a bibTex. “<b>Symptom Questionnaire_Redacted.pdf</b>”: This is a copy of the electronic questionnaire patients with an upper respiratory symptoms were required to fill out. All identifying information has been redacted. “<b>DataDictionary_VirulenceTradeOff.xlsx</b>”: This document provides a description of all the variables included in the analysis. “<b>1 Anonymized Data</b>” folder contains the de-identified data for the analyses An R script that merges all of the individual data sets and creates and saves “Data.Rda” and “Data.csv” in the “1 Anonymized Data” Folder. This script is not included since the raw data sets are not included to protect patient privacy. “<b>2 Data Cleaning Script</b>” folder contains one R script that cleans the data for the analyses “<b>Data Merging Script.R</b>”: R script that merges all of the individual data sets and creates and saves “Data.Rda” in the “1 Anonymized Data” Folder. This script is not included since the raw data sets are not included to protect patient privacy. “<b>Data Cleaning.R</b>”: This R script does all of the data preparation, creating all the required variables for the analysis. This script also produces the data sets used for the analyses and saves them in the “3 Clean Data” folder. “<b>4 Analysis Scripts</b>” folder has 4 R scripts that analyze the clean data and produce the results presented in the main text and supplement. “<b>Flu Symptoms Activity Models.R</b>” This script creates the univariate/multivariate linear regression table, the Spearman rank correlation, and the CMH trend tests. Results are saved in “5 Results” “<b>Flu Symptoms Activity Plots.R</b>” This script creates all of the plots. Results are saved in “5 Results” “<b>Flu Symptoms Activity Tables.R</b>” This script creates all of the tables. Results are saved in “5 Results” “<b>Multivariate Subset Selection.R</b>” This script does the variable selection for the multivariate model. Results are saved in “5 Results” “<b>6 Manuscript</b>” folder has 2 files in it used to create the manuscript. “<b>Manuscript.Rmd</b>” This Rmd file creates the basic manuscript word document (formatting will not be identical) “<b>proceedings-of-the-royal-society-b.csl</b>” is a style file to format the citations in the manuscript “<b>7 Supplemental Material</b>” folder has 2 files used to create this document “<b>Supplemental Material.Rmd</b>” This Rmd file creates the basic supplemental material word document (formatting will not be identical) “<b>proceedings-of-the-royal-society-b.csl</b>” is a style file to format the citations in the supplement <strong>Reproducing The Results</strong> The files required to reproduce the results are 2 R Markdown files, 4 R script, and one anonymized data file. These files allow the reproduction of all results shown in the main text and SM. To reproduce the results follow these steps. First, install R, Rstudio, and Pandoc (when you install Rstudio Pandoc should automatically install). Microsoft Word or Open Office Word is also required. Second, save the zip file from Dryad on your local computer. Open the folder and double click “Virulence_Trade-off”. This should open Rstudio (if prompted, select Rstudio as the app to open this file type). Then open and run the files below in the specified order. R script “Data Cleaning.R” in the “2 Data Cleaning Script” folder uses “Data.Rda” and produces two clean data sets used for all further analyses. The data sets are all saved in the “3 Clean Data” folder and include: “SympAct_Any_Pos.Rda” Contains data for all influenza patients regardless of diagnosis method. “SympAct_Lab_Pos.Rda” Contains data for influenza patients diagnosed based on a PCR or rapid antigen test. <b>It is important to note that “SympAct_Lab_Pos.Rda” is a subset of “SympAct_Any_Pos.Rda” based on the method of diagnosis.</b> Four R scripts in the “4 Analysis Scripts” folder (“Flu Symptoms Activity Univariate Model.R”, “Flu Symptoms Activity Univariate Plots.R”, and “Flu Symptoms Activity Univariate Tables.R”, “Multivariate Subset Selection.R”). The order you run these scripts does not matter. Results of each script are automatically saved in the “5 Results” folder. R Markdown “Manuscript.Rmd” is in the “6 Manuscript” folder. This combines all the relevant results and creates the main text as a Word document (some reformatting is required). R Markdown “Supplemental Material.Rmd” in the “7 Supplemental Material” folder generates the supplementary material as Word document.