Facilitation through altered resource availability in a mixed-species rodent malaria infection.

A major challenge in disease ecology is to understand how co-infecting parasite species interact. We manipulate in vivo resources and immunity to explain interactions between two rodent malaria parasites, Plasmodium chabaudi and P. yoelii.

Ecological influences on the behaviour and fertility of malaria parasites.

Background: Sexual reproduction in the mosquito is essential for the transmission of malaria parasites and a major target for transmission-blocking interventions. Male gametes need to locate and fertilize females in the challenging environment of the mosquito blood meal, but remarkably little is known about the ecology and behaviour of male gametes.

Methods: Here, a series of experiments explores how some aspects of the chemical and physical environment experienced during mating impacts upon the production, motility, and fertility of male gametes.

Existing Infection Facilitates Establishment and Density of Malaria Parasites in Their Mosquito Vector.

Very little is known about how vector-borne pathogens interact within their vector and how this impacts transmission. Here we show that mosquitoes can accumulate mixed strain malaria infections after feeding on multiple hosts. We found that parasites have a greater chance of establishing and reach higher densities if another strain is already present in a mosquito.

Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring.

Artemisinin-based drugs are the front-line weapon in the treatment of human malaria cases, but there is concern that recent reports of slow clearing infections may signal developing resistance to treatment. In the absence of molecular markers for resistance, current efforts to monitor drug efficacy are based on the rate at which parasites are cleared from infections. However, some knowledge of the standing variation in parasite susceptibility is needed to identify a meaningful increase in infection half-life.

The path of least resistance: aggressive or moderate treatment?

The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance.

Rapid response to selection, competitive release and increased transmission potential of artesunate-selected Plasmodium chabaudi malaria parasites.

The evolution of drug resistance, a key challenge for our ability to treat and control infections, depends on two processes: de-novo resistance mutations, and the selection for and spread of resistant mutants within a population. Understanding the factors influencing the rates of these two processes is essential for maximizing the useful lifespan of drugs and, therefore, effective disease control. For malaria parasites, artemisinin-based drugs are the frontline weapons in the fight against disease, but reports from the field of slower parasite clearance rates during drug treatment are generating concern that the useful lifespan of these drugs may be limited.

Stress and sex in malaria parasites: Why does commitment vary?

For vector-borne parasites such as malaria, how within- and between-host processes interact to shape transmission is poorly understood. In the host, malaria parasites replicate asexually but for transmission to occur, specialized sexual stages (gametocytes) must be produced. Despite the central role that gametocytes play in disease transmission, explanations of why parasites adjust gametocyte production in response to in-host factors remain controversial.

Mosquito transmission, growth phenotypes and the virulence of malaria parasites.

Background: A series of elegant experiments was recently published which demonstrated that transmission of malaria parasites through mosquitoes elicited an attenuated growth phenotype, whereby infections grew more slowly and reached peak parasitaemia at least five-fold lower than parasites which had not been mosquito transmitted. To assess the implications of these results it is essential to understand whether the attenuated infection phenotype is a general phenomenon across parasites genotypes and conditions.

Methods: Using previously published data, the impact of mosquito transmission on parasite growth rates and virulence of six Plasmodium chabaudi lines was analysed.

Costs of crowding for the transmission of malaria parasites.

The utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. However, integrating evolutionary ecology and infectious disease epidemiology is challenging because within-host dynamics can have counterintuitive consequences for between-host transmission, especially for vector-borne parasites. A major obstacle to linking within- and between-host processes is that the drivers of the relationships between the density, virulence, and fitness of parasites are poorly understood.

The problem of auto-correlation in parasitology.

Explaining the contribution of host and pathogen factors in driving infection dynamics is a major ambition in parasitology. There is increasing recognition that analyses based on single summary measures of an infection (e.g.

The meaning of death: evolution and ecology of apoptosis in protozoan parasites.

The discovery that an apoptosis-like, programmed cell death (PCD) occurs in a broad range of protozoan parasites offers novel therapeutic tools to treat some of the most serious infectious diseases of humans, companion animals, wildlife, and livestock. Whilst apoptosis is an essential part of normal development, maintenance, and defence in multicellular organisms, its occurrence in unicellular parasites appears counter-intuitive and has proved highly controversial: according to the Darwinian notion of "survival of the fittest", parasites are expected to evolve strategies to maximise their proliferation, not death. The prevailing, and untested, opinion in the literature is that parasites employ apoptosis to "altruistically" self-regulate the intensity of infection in the host/vector.

Competition and the evolution of reproductive restraint in malaria parasites.

All organisms must trade off resource allocation between different life processes that determine their survival and reproduction. Malaria parasites replicate asexually in the host but must produce sexual stages to transmit between hosts. Because different specialized stages are required for these functions, the division of resources between these life-history components is a key problem for natural selection to solve.

Malaria and trypanosome transmission: different parasites, same rules?

African trypanosomes produce different specialized stages for within-host replication and between-host transmission and therefore face a resource allocation trade-off between maintaining the current infection (survival) and investment into transmission (reproduction). Evolutionary theory predicts the resolution of this trade-off will significantly affect virulence and infectiousness. The application of life history theory to malaria parasites has provided novel insight into their strategies for survival and reproduction; how this framework can now be applied to trypanosomes is discussed.

Investigating the evolution of apoptosis in malaria parasites: the importance of ecology.

Apoptosis is a precisely regulated process of cell death which occurs widely in multicellular organisms and is essential for normal development and immune defences. In recent years, interest has grown in the occurrence of apoptosis in unicellular organisms. In particular, as apoptosis has been reported in a wide range of species, including protozoan malaria parasites and trypanosomes, it may provide a novel target for intervention.

Temporal patterns in immune responses to a range of microbial insults (Tenebrio molitor).

Much work has elucidated the pathways and mechanisms involved in the production of insect immune effector systems. However, the temporal nature of these responses with respect to different immune insults is less well understood. This study investigated the magnitude and temporal variation in phenoloxidase and antimicrobial activity in the mealworm beetle Tenebrio molitor in response to a number of different synthetic and real immune elicitors.