Parasite responses to interventions

Drug resistance is a major obstacle to controlling infectious diseases. Ensuring the continued efficacy of drugs requires early and rapid detection of resistance, and containment of its spread. Ideally, resistance would be detected when it is at a low level (drug ‘tolerance’) and low frequency in a patient, well before it has become a clinical problem. A key challenge for early resistance detection is that little can be known in advance about the mechanisms underlying it and, frequently, resistance mechanisms involve loci other than those encoding drug targets. Along with our collaborators, we are working on new approaches for detecting resistance that capitalizes on evolutionary and ecological insights and looks instead for a phenotypic signature of resistance.

Given challenges like drug resistance, one of the most important questions in disease ecology and evolution is “how do we make medical interventions evolution-proof?” But emerging data suggests that plasticity in life history traits is another tool that parasites have at their disposal to evade the efforts of biomedicine. In experimental infections – where host genetics, age, sex and a suite of other environmental variables are highly controlled – a considerable amount of plasticity is observed. There is every reason to expect, then, that plasticity in natural infections will be an important aspect of how parasites evade our control. So, should we also be asking how to make interventions plasticity-proof? We are developing mathematical models to explore the clinical, epidemiological, and evolutionary consequences of parasite plasticity in response to interventions and to determine the conditions under which such plasticity facilitates or constrains intervention-driven evolution.

Relevant papers:

Huijben, S., Bell, A.S., Sim, D.G., Tomasello, D., Mideo, N., Day, T., & Read, A.F. (2013) Aggressive chemotherapy and the selection of drug resistant pathogens. PLoS Pathogens, 9: e1003578.PDF

Mideo, N., Kennedy, D.A., Carlton, J.M., Bailey, J.A., Juliano, J.J., & Read, A.F. (2013) Ahead of the curve: Next-generation estimators of drug resistance in malaria infections. Trends in Parasitology, 29: 321-328.PDF

Mideo N., & Reece S.E. (2012) Plasticity in parasite phenotypes: evolutionary and ecological implications for disease. Future Microbiology, 7: 17-24.PDF