Evolution Highlight: Virulence-driven trade offs in disease transmission

Each month, the Evolution Highlights series will highlight some of the interesting and varied papers published within the last few years in Evolution. The goal of these Evolution Highlights is to let our readers learn more about how the highlighted study came into existence, and to invite the authors to share stories and tips from the perspective of a recently published author. We welcome nominations and self-nominations for the Evolution Highlights. Find out how to submit a paper here.

The words Evolution Highlight in white on a yellow box above the paper title and author list in white on a dark blue background showing digital drawings of spherical viruses

"Virulence-driven trade offs in disease transmission: A meta-analysis"
Acevedo, M. A., Dillemuth, F. P., Flick, A. J., Faldyn, M. J., & Elderd, B. D. (2019). Virulence‐driven trade‐offs in disease transmission: A meta‐analysis. Evolution, 73(4), 636-647.
https://onlinelibrary.wiley.com/doi/full/10.1111/evo.13692

Abstract:
The virulence–transmission trade-off hypothesis proposed more than 30 years ago is the cornerstone in the study of host–parasite co-evolution. This hypothesis rests on the premise that virulence is an unavoidable and increasing cost because the parasite uses host resources to replicate. This cost associated with replication ultimately results in a deceleration in transmission rate because increasing within-host replication increases host mortality. Empirical tests of predictions of the hypothesis have found mixed support, which cast doubt about its overall generalizability. To quantitatively address this issue, we conducted a meta-analysis of 29 empirical studies, after reviewing over 6000 published papers, addressing the four core relationships between (1) virulence and recovery rate, (2) within-host replication rate and virulence, (3) within-host replication and transmission rate, and (4) virulence and transmission rate. We found strong support for an increasing relationship between replication and virulence, and replication and transmission. Yet, it is still uncertain if these relationships generally decelerate due to high within-study variability. There was insufficient data to quantitatively test the other two core relationships predicted by the theory. Overall, the results suggest that the current empirical evidence provides partial support for the trade-off hypothesis, but more work remains to be done.

Evolution Highlight by Miguel Acevedo
Wildlife Ecology and Conservation, University of Florida

What gave you the idea for this study?

Questions about virulence—the negative consequences a parasite has on individual fitnesscould be traced back to Pasteur’s experiments in the 19th century showing that virulence is not a fixed trait. But maybe it was the theoretical formulations of Anderson and May in the ’80s that sparked the interest of the community. Multiple studies have studied virulence in the context of the transmission-virulence trade-off. With some studies finding support and others not, there was no consensus. So, we decided to tackle the problem using a meta-analysis approach.

What was the big question you were trying to ask and why was it exciting?

Overall, we were interested in answering the question: Is there enough evidence to generalize predictions from the transmission-virulence trade-off hypothesis? The theoretical predictions from Anderson and May’s model are central to disease ecology and evolution. Finding overwhelming empirical support would suggest that the theory is general and robust. If not, it may suggest that the theory needs to be re-evaluated. Alternatively, if we found that there were not enough studies to conclude, we could guide future studies to address key knowledge gaps.

In what ways does this study expand or build on your previous studies?

Well, in a way we could say that this study is literally made from previous studies! :) It is a meta-analysis which means that we re-analyzed data from previous studies to test for generalizable patterns.

From your perspective, what was the most interesting or intriguing aspect of this study?

By searching from thousands of papers we got a pretty good perspective on the dramatic divorce between theoretical and empirical studies. The theory advanced way faster.

Were there any unexpected logistical or technical challenges you had to address?

It was a meta-analysis, so I’ll guess the answer is yes! First, we analyze together data from studies that were not initially designed to be analyzed in that way. Second, the trade-off hypothesis predicts that the relationship between transmission and virulence “decelerates” with increasing virulence. But, what kind of functional relationship is expected to decelerate? Third, the inclusion criteria were difficult to automate so our team had to patiently screen manually thousands of papers.

Did your work take you to any interesting locations? If so, what were they like?

Unfortunately, since it was a meta-analysis the study was conducted pretty much on a computer. But I got to work in pretty good coffee shops. :)

Did you have to learn any new analytical techniques for this study?

A big challenge of our study was how to consistently test for a “deceleration” in the relationship between transmission and virulence in different studies. As a team, we discussed multiple approaches. But it turned out to be difficult to do it extracting effect sizes directly from studies. Finally, we decided on an “individual-patient data” approach because it allowed us to re-analyze the data from all studies in a consistent way. Interestingly, there were less than a handful of studies designed this way in ecology and evolution.

What was your writing process like?

That’s a great question. Right before writing this paper, I finished reading “Writing Science” by J. Schimel. In a way, this was my first real-life practice applying some of the tricks I learned from the book.

We started with the figures and the results, then the methods, then the discussion and constructed the introduction right at the end. This really helped us craft a concise story with all the details needed to understand and replicate it, but not more.

What was the biggest challenge about writing the manuscript?

There have been some previous great reviews on the trade-off hypothesis, so we didn’t want to replicate that. Therefore, we had to balance providing enough context for the reader to understand the background and the need for the study without necessarily doing an extensive review of the topic.

Was this study collaborative with other groups? If so, what was valuable about that experience?

This was a whole lab effort. It was a great honor to collaborate with such a great group of scientists. Now remembering how this study was conceived made me realized that everybody now has moved on to do big and better things, and how I miss everybody.

How would you explain your study to a five-year-old?

Diseases make people sick. But some diseases make you sicker than others. They get passed from person to person and some think that some of the diseases that get passed more than others can make you sicker. We studied that and found that…for the most part…we still don’t know :)

 
 
 
 
 
 
 
 
 
 
Two men standing on either side of a poster in a conference hall. The men are smiling at the camera and wearing name tags.


Back to top