Daily rhythms: drivers of parasite-vector interactions and parasite evolution

The Earth’s daily rotation dictates the timing of activities for almost all organisms and is assumed to explain the evolution of circadian clocks and daily rhythms. However, the evolutionary ecology of rhythms is poorly understood, especially for parasites/pathogens, for whom the environments experienced inside hosts and vectors changes dramatically over 24 hours. Yet, rhythms play fundamental roles during infections; for example, the time-of-day an infection is acquired by organisms as diverse as insects and mammals can determine whether they survive or succumb. Daily rhythms exhibited by hosts/vectors also affect the fitness of the parasites/pathogens they transmit. This includes the costs of time-of-day dependent dangers imposed by immune rhythms, and the benefits of time-of-day specific opportunities, such as the influx of nutrients available to parasites/pathogens following the rhythmic foraging of the host/vector. Yet, how parasites/pathogens cope with the constraints of environmental rhythms and exploit rhythmic opportunities, is a fundamental knowledge gap in understanding the evolutionary ecology of infections. Addressing this neglected aspect of infections is critical for vector-borne diseases because the activities of insect vectors – which are highly sensitive to rhythms in the abiotic environment – dictate the time-of-day that parasites/pathogens transmit and complete their lifecycles. Thus, we will push the frontiers by using the model system of Anopheline mosquitoes and malaria (Plasmodium) parasites to uncover how daily rhythmicity in transmission opportunities affects vectorial capacity, infection spread, and parasite evolution. Specifically, we will use field and lab experiments coupled with theoretical modelling to test hypotheses derived from integrating concepts of life history evolution with chronobiology and parasitology. First, we will quantify variation in the time-of-day that wild Anopheline mosquito vectors forage for blood (bite), uncover the environmental and physiological factors that generate variation between mosquitoes in biting time-of-day, and experimentally determine the consequences of different blood feeding times for survival, biting rate, and fecundity. Knowing how many, and what kinds of, vectors bite at different times of day will uncover the roles of rhythms in vectorial capacity. Second, we will test how biting time-of-day affects Plasmodium infection rate and proliferation within mosquitoes, and transmission to subsequent hosts. We will integrate these rhythms into the well-established theoretical framework for predicting malaria parasite fitness (R0) to estimate time-of-day-dependent transmission rates, identify which rhythms are the most influential for transmission, and predict the epidemiological consequences of shifts in biting rhythms. Uncovering which rhythms matter, and explaining why, for malaria transmission is urgently needed because malaria-transmitting mosquitoes are shifting when they bite. Third, we will reveal how parasites adapt in response to shifts in biting time-of-day. We will do this by experimentally evolving parasites through sequential cycles of host-vector-host transmission at the classical time-of-day (in the middle of the night) or at early, late, and erratic times of day for transmission, and comparing the resulting phenotypes (traits underpinning within- and between-host fitness) across treatments. Parasites express their own rhythms which exhibit genetic and environmental variation and so, identifying their evolutionary potential is central to predicting the short- and long-term consequences of the anthropogenic forces disrupting vector rhythms. By opening up a neglected aspect of the evolutionary ecology of infections, we bring a novel perspective to the NERC’s Environmental and Social Ecology of Human Infectious Diseases initiative, and will inform how to protect health, disrupt transmission, and identify intervention targets for a major disease.