CIDD has the personnel to do some amazing work on cross-scale disease dynamics, but it’s not always clear how to relate within- and between-host processes. People researching within-host processes may not understand the sorts of questions that researchers working between hosts will hone in on as important, and vice-versa. In this post, I ask ten questions whose answers would really improve how I think about the interface between immunology and epidemiology. I’d love to see other people’s lists; these are just my off-the-cuff, post-CIDD-lunch (highly-hyphenated) initial attempts.
Before I begin, here’s my basic premise. I think there are three links relating what happens within the host to what happens between hosts. These are
1. How (and how long, and at what intensity) does the pathogen persist in the host?
2. How does pathogen load (+ other load-related within-host processes) map to transmission between hosts?
3. How does pathogen load (+ other load-related within-host processes) map to disease-induced mortality?
Since I work on wildlife, I don’t have the luxury of actually studying any given system in great detail (read: my animals don’t survive in pens). As a consequence, I’m on an on-going quest for general motifs within the host that I could apply to different systems, to think what’s driving population-level epidemiology.
These motifs are hard to identify (especially for the immunological illiterati such as myself)! But I’m an optimist, so I’m putting these out there as a wish-list for public consumption. The wording is intentionally simplistic, an admittedly serious transgression; I hope you’ll forgive.
Lots of people are working on these questions already. Some are stolen from other places, and some probably even have clear, published answers. My point isn’t so much that these specific questions are the “right” ones, but rather that they’re the sort of questions on the research horizon that we at CIDD are uniquely equipped to tackle.
So, without further ado:
1. When (both epidemiologically and immunologically) can we treat a host as a well-mixed unit, and in what situations should we be particularly concerned about spatial structure within the host? When do we expect immune-privileged sites to have major implications on epidemiological processes?
2. Should we think about population-level epidemiology of pathogens with primarily mucosal vs. primarily humoral immune responses in fundamentally different ways?
3a. Are there general motifs of pathogen dynamics within the host, and how those motifs map to transmission and disease-induced mortality rates? Do classic predator-prey functional response models within the host (e.g., host immune defenses “prey on” pathogen load) actually make sense, or are they just stand-ins until we know better?
3b. Under what conditions will our epidemiological understanding benefit from incorporating these general motifs into population-level models? What motifs do we actually know well-enough to incorporate?
4. How do we map from the ecological definition of “tolerance” (e.g. – loosely – host fitness is independent of pathogen load) to the immunological one (e.g. – again, loosely – host does not mount an immune response to the pathogen)? What’s going on in systems where we see ecological tolerance, but not immunological tolerance? Would considering high- and low-zone tolerance improve some population-level epidemiological models? For what systems?
5. Are there general mechanisms underlying chronic carriage, and can we build any systematic expectations about when chronic carriage maps to chronic shedding (e.g., when do carriers transmit)? Also, are there cases when we can predict who’s carrying, and how accurate are those predictions?
6. What is the relative importance of host behavior and within-host dynamics in determining who’s a super-spreader? Does this vary systematically between systems?
7. I hear that sometimes I should think about other within-host processes besides just immune response relating to transmission. Are there particular kinds of pathogens where that’s likely to be true? What other within-host systems should I worry about? How does the function of those systems relate to pathogen persistence and transmission, and disease-induced mortality? Are there general themes here??
8. How do we best use existing immunology to think about co-infection? Do we have a basis for moving past a world-view focused on Th1/Th2 trade-offs?
9. Also, do we expect that Th17 and Tregs have major epidemiological implications in some cases? Which cases, and how?
10. What epidemiological inferences can we back out of serology data, and could we learn a lot more? When is it worthwhile to parse IgG from IgA from IgM? How much additional information would that give us to estimate force of infection? (inspired by the RAPIDD serology workshop, Jan 2015).
Obviously, I’m overlooking a lot here (maternal immunity, environmental effects, etc.), simplifying a ton, and asking for knowledge that may not yet exist. What have I ruthlessly overlooked, or horrifically oversimplified? Where are the other big gaps? What should I REALLY be writing my dissertation about?
Most importantly, what is the complementary set of questions from someone with a within-host perspective?