The Metcalf lab focuses on two areas of research:
a) Characterizing the landscape of immunity to support public health, and
b) Developing a framework for understanding the evolution of immune function.
The landscape of immunity is shaped by vaccination and natural infection. Characterizing immunity acquired via vaccination coverage is core to targeting and reinforcing public health efforts, and yet considerable uncertainty remains. The Metcalf lab has helped develop techniques for evaluating spatial heterogeneity in vaccination coverage, and exploring its consequences in the context of a major disruption (eg. ebola outbreak). In the context of natural infection, human movement shapes both the introduction of pathogens into unaffected populations, but can also shape major movements of susceptible individuals – aggregation can create conditions favorable to increasing transmission and large outbreaks. We utilize novel data-streams such as mobile phone call data records to capture both the patterns of seasonal human aggregation and its effects on transmission for directly transmitted pathogens (measles, rubella), but also patterns of local introduction for a broader range of infections (measles to malaria) for a range of countries and contexts. Patterns of re-introduction are of increasing relevance in a public health landscape where disease elimination and eradication remain a central concern.
Climatic drivers may shape both human movement and pathogen ecology, and we are working on describing the climate influences on human movement at a range of scales and to titrate the relative importance of these direct and indirect effects for a range of pathogens. This will open the way to longer term predictions of the outcome of climate change on human movement and the burden of infectious disease. To date, we have revealed the driving force of human aggregation for rubella dynamics in Kenya and are expanding this analysis across pathogens and contexts to encompass the effects of human movement on measles control in Pakistan and malaria in Madagascar. Seasonal human movement is a focus of this research thread and we are working with collaborators to build links to climate phenomenon.
Individual immunity is a powerful force and one whose effects can scale up to affect pathogen transmission dynamics and the disease burden for entire populations (a process underlying the concept of herd immunity). Despite this importance, the fundamental drivers of immune function remain obscure, partly as a result of challenges in articulating and estimating the core trade-offs that shape immunity. The Metcalf lab has been working to identify tractable sub-questions in this area, such as the evolution of the timing of maternal immunity, but also to extend previously developed methods to model within host dynamics with the aim of providing insight into key effectors and mechanisms that can then be considered in a broader evolutionary context. The lab also works on theoretical models considering the microbiome; it is increasingly recognized that microbiota can play a key role in host defense, a natural extension in considering the evolution of immune function.