RE-EMERGING INFECTIOUS DISEASES: THE CHALLENGE AND OPPORTUNITY OF PERTUSSIS
Abstract: Complex systems paradigms, such as critical slowing down, regime shifts, systems theory, and computational forecasting, have taken center stage in the global effort to predict and mitigate emerging and re-emerging infectious diseases. Such approaches are predicated on models integrating information collected typically at microscopic scales and extrapolating macro-scale phenomena, such as bifurcation, percolation, and persistence. Complex systems perspectives and methodologies are essential as we come to grips with the ecology, immunology, and evolution of complicated infectious disease systems. Pertussis offers a prime example of this in the context of a scientific problem of great timeliness and importance.
The current re-emergence of pertussis, once seemingly on track to eradication, is enigmatic, due largely to its complexity as a host/pathogen system. In particular, the dynamics of pertussis are shaped by the interplay of pathogen transmission, host immunity, host contact-network structure, pathogen evolution, and public-health intervention across a wide range of spatio-temporal scales and levels of biological organization. Globally, trends and cycles in pertussis prevalence are idiosyncratic, due to variations in human behavior, geographic transmission bottlenecks, and dynamic variation in the nature and extent of public health intervention. The resulting scientific contention can only be resolved by theory capable of reconciling disparate, and seemingly contradictory, observations. Key elements of such a theory necessarily include: heterogeneities in immunity, age- and spatially-structured contact networks, dynamism in contact-network structure at behavioral time-scales, and large exogenous perturbations due to vaccination campaigns and behavior changes. Simplified versions of such theoretical systems display (1) prolonged transient dynamics which can contain signatures of the mode and efficacy of immunological protection, (2) sensitivity to contact-network structure, (3) prominent interactions between nonlinear and stochastic effects, and (4) manifold potential for counterintuitive emergent effects resulting from the above. The intellectual aim of the workshop will be to develop a complex-systems theory of pertussis within an inferential framework suitable for confronting models directly with extant data drawn from epidemiology, behavior, and immunology. This theory, and the techniques used to test it, will be readily generalizable to other disease systems because our efforts to resolve the causes and consequences of pertussis’ resurgence will necessarily be focused on the essential theoretical questions at issue in complex eco-epidemiological systems generally.
In June, I had the opportunity to spend two weeks in Princeton working with Andrea Graham and two postdocs, Sarah Budischak and Anieke van Leeuwen. The purpose of this visit was two-fold: (1) develop a mathematical model of within-host dynamics incorporating host immune responses, non-immune physiological processes (e.g., growth, storage), and parasite exploitation and growth; (2) use this model as a basis for identifying key experimental measurements to quantify the effect of diet on host and parasite fitness. This exchange stemmed from a theory paper I published last year showing that increased host resources could either increase or decrease parasite fitness, depending on the structure of the resource-immune-parasite interaction. Dr. Graham and Dr. Budischak initially contacted me to ask about extending the model to consider the role of host diet in driving within-host dynamics of macroparasites, focusing on understanding when host response should focus on tolerance over resistance. Out of this conversation, I developed an RCN proposal more broadly considering how diet links within-host and between-host scales to shape both host immune phenotype and parasite exploitation.
The research exchange was structured around daily meetings between the four of us. I would typically spend the day working in Dr. Graham’s lab alongside Dr. Budischak, who is primarily trained as an immunologist. This work environment allowed me to get instantaneous feedback as I was developing the model. During the first week of the exchange, the daily meetings were primarily spent defining, discussing, defending, and refining a biologically reasonable model structure. This was one of the most useful aspects of the process for me, as my knowledge of immunology is limited. As the model development proceeded, Dr. Budischak searched the biomedical literature for estimates of model parameters. This process helped identify key parameters that need to be quantified from subsequent Graham lab experiments. During the second week of the exchange, the focus shifted to model analysis (both analytical and numerical). This analysis helped further hone the search for parameter values and showed that the model is capable of producing both host tolerance and host resistance.
I am hopeful (and reasonably confident) that this research exchange has resulted in a profitable long-term collaboration. Already we have used results from this exchange in two grant proposals. The current plan is to use the data from mouse-helminth experiments to develop an empirically validated model of within-host dynamics and then use this model to study the ecological and evolutionary dynamics of both the host and parasite, focusing on questions like: (1) can diet shift parasites from being resource-limited to immune-limited, and does each type of limitation have a dynamical signature at the between-host scale? and (2) when do cross-scale interactions give rise to self-reinforcing feedbacks, such as the “negative spiral” of malnutrition and infection?
The Odum School of Ecology at the University of Georgia is initiating a new track for doctoral training in Interdisciplinary Disease Ecology Across Scales. A postdoctoral associate is being sought to assist with curriculum development, student evaluation, and assessment.
Applicants must have a Ph.D. in either (1) ecology, evolution, or other field related to infectious disease biology (e.g., immunology, microbiology) or (2) education (with a strong emphasis and background in biology). Applicants are expected to have experience or a genuine interest in instruction, education research, or evaluation and assessment at the post-secondary level.
For more details about the position and how to apply please visit: