The epidemiology of vector‐borne pathogens is largely determined by the host‐choice behaviour of their vectors. Here, we investigate whether a Plasmodium infection renders the host more attractive to ...host‐seeking mosquitoes. For this purpose, we work on a novel experimental system: the avian malaria parasite Plasmodium relictum, and its natural vector, the mosquito Culex pipiens. We provide uninfected mosquitoes with a choice between an uninfected bird and a bird undergoing either an acute or a chronic Plasmodium infection. Mosquito choice is assessed by microsatellite typing of the ingested blood. We show that chronically infected birds attract significantly more vectors than either uninfected or acutely infected birds. Our results suggest that malaria parasites manipulate the behaviour of uninfected vectors to increase their transmission. We discuss the underlying mechanisms driving this behavioural manipulation, as well as the broader implications of these effects for the epidemiology of malaria.
The emergence and re-emergence of pathogens remains a major public health concern. Unfortunately, when and where pathogens will (re-)emerge is notoriously difficult to predict, as the erratic nature ...of those events is reinforced by the stochastic nature of pathogen evolution during the early phase of an epidemic. For instance, mutations allowing pathogens to escape host resistance may boost pathogen spread and promote emergence. Yet, the ecological factors that govern such evolutionary emergence remain elusive because of the lack of ecological realism of current theoretical frameworks and the difficulty of experimentally testing their predictions. Here, we develop a theoretical model to explore the effects of the heterogeneity of the host population on the probability of pathogen emergence, with or without pathogen evolution. We show that evolutionary emergence and the spread of escape mutations in the pathogen population is more likely to occur when the host population contains an intermediate proportion of resistant hosts. We also show that the probability of pathogen emergence rapidly declines with the diversity of resistance in the host population. Experimental tests using lytic bacteriophages infecting their bacterial hosts containing Clustered Regularly Interspaced Short Palindromic Repeat and CRISPR-associated (CRISPR-Cas) immune defenses confirm these theoretical predictions. These results suggest effective strategies for cross-species spillover and for the management of emerging infectious diseases.
Malaria parasites have been shown to adjust their life history traits to changing environmental conditions. Parasite relapses and recrudescences--marked increases in blood parasite numbers following ...a period when the parasite was either absent or present at very low levels in the blood, respectively--are expected to be part of such adaptive plastic strategies. Here, we first present a theoretical model that analyses the evolution of transmission strategies in fluctuating seasonal environments and we show that relapses may be adaptive if they are concomitant with the presence of mosquitoes in the vicinity of the host. We then experimentally test the hypothesis that Plasmodium parasites can respond to the presence of vectors. For this purpose, we repeatedly exposed birds infected by the avian malaria parasite Plasmodium relictum to the bites of uninfected females of its natural vector, the mosquito Culex pipiens, at three different stages of the infection: acute (∼ 34 days post infection), early chronic (∼ 122 dpi) and late chronic (∼ 291 dpi). We show that: (i) mosquito-exposed birds have significantly higher blood parasitaemia than control unexposed birds during the chronic stages of the infection and that (ii) this translates into significantly higher infection prevalence in the mosquito. Our results demonstrate the ability of Plasmodium relictum to maximize their transmission by adopting plastic life history strategies in response to the availability of insect vectors.
Some Plasmodium species have the ability to modify the behaviour of their mosquito vectors. This is thought to be an adaptive strategy that maximizes the parasite's transmission.
The effect of ...Plasmodium relictum infections on the blood feeding behaviour of Culex pipiens quinquefasciatus mosquitoes was monitored.
Plasmodium infections did not alter the proportion of blood fed mosquitoes but they did affect the dynamics and the size of the blood meal. Sporozoite-infected mosquitoes completed their blood meal 1.3 times later than uninfected mosquitoes and ended up with smaller blood meals.
The potential adaptive nature of this manipulation of mosquito behaviour is discussed in the light of previous studies on other malaria models.
The control of most vectors of malaria is threatened by the spread of insecticide resistance. One factor that has been hitherto largely overlooked is the potential effects of insecticide resistance ...on the ability of mosquitoes to transmit malaria: are insecticide-resistant mosquitoes as good vectors of Plasmodium as susceptible ones? The drastic physiological changes that accompany the evolution of insecticide resistance may indeed alter the ability of vectors to transmit diseases, a possibility that, if confirmed, could have major epidemiological consequences.
Using a novel experimental system consisting of the avian malaria parasite (Plasmodium relictum) and its natural vector (the mosquito Culex pipiens), two of the most common mechanisms of insecticide resistance (esterase overproduction and acetylcholinesterase modification) were investigated for their effect on mosquito infection rate and parasite burden. For this purpose two types of experiments were carried out using (i) insecticide-resistant and susceptible laboratory isogenic lines of Cx. pipiens and (ii) wild Cx. pipiens collected from a population where insecticide resistant and susceptible mosquitoes coexist in sympatry.
The isogenic line and wild-caught mosquito experiments were highly consistent in showing no effect of either esterase overproduction or of acetylcholinesterase modification on either the infection rate or on the oocyst burden of mosquitoes. The only determinant of these traits was blood meal size, which was similar across the different insecticide resistant categories in both experiments.
Insecticide resistance was found to have no effect on Plasmodium development within the mosquito. This is the first time this question has been addressed using a natural mosquito-Plasmodium combination, while taking care to standardize the genetic background against which the insecticide resistance genes operate. Infection rate and oocyst burden are but two of the factors that determine the vectorial capacity of mosquitoes. Other key determinants of parasite transmission, such as mosquito longevity and behaviour, or the parasite's incubation time, need to be investigated before concluding on whether insecticide resistance influences the ability of mosquitoes to transmit malaria.
BACKGROUND: Identifying the parasites transmitted by a particular vector and the factors that render this vector susceptible to the parasite are key steps to understanding disease transmission. ...Although avian malaria has become a model system for the investigation of the ecological and evolutionary dynamics of Plasmodium parasites, little is still known about the field prevalence, diversity and distribution of avian Plasmodium species within the vectors, or about the extrinsic factors affecting Plasmodium population dynamics in the wild. METHODS: We examined changes in avian malaria prevalence and Plasmodium lineage composition in female Culex pipiens caught throughout one field season in 2006, across four sampling sites in southern France. Using site occupancy models, we correct the naive estimates of Plasmodium prevalence to account for PCR-based imperfect detection. To establish the importance of different factors that may bear on the prevalence and diversity of avian Plasmodium in field mosquitoes, we focus on Wolbachia and filarial parasite co-infections, as well as on the insecticide resistance status of the mosquito. RESULTS: Plasmodium prevalence in Cx. pipiens increased from February (0%) to October (15.8%) and did not vary significantly among the four sampling sites. The application of site occupancy models leads to a 4% increase in this initial (naive) estimate of prevalence. The parasite community was composed of 15 different haemosporidian lineages, 13 of which belonged to the Plasmodium genus, and 2 to the Haemoproteus genus. Neither the presence of different Wolbachia types and of filarial parasites co-infecting the mosquitoes, nor their insecticide resistance status were found to affect the Plasmodium prevalence and diversity. CONCLUSION: We found that haemosporidian parasites are common and diverse in wild-caught Cx. pipiens mosquitoes in Southern France. The prevalence of the infection in mosquitoes is unaffected by Wolbachia and filarial co-infections as well as the insecticide resistant status of the vector. These factors may thus have a negligible impact on the transmission of avian malaria. In contrast, the steady increase in prevalence from February to October indicates that the dynamics of avian malaria is driven by seasonality and supports that infected birds are the reservoir of a diverse community of lineages in southern France.
Mutations allowing pathogens to escape host immunity promote the spread of infectious diseases in heterogeneous host populations and can lead to major epidemics. Understanding the conditions that ...slow down this evolution is key for the development of durable control strategies against pathogens. Here, we use theory and experiments to compare the efficacy of three strategies for the deployment of resistance: (i) a
strategy where the host population contains two single-resistant genotypes, (ii) a
strategy where the host carries a double-resistant genotype, (iii) a
strategy where the host population is a mix of a single-resistant genotype and a double-resistant genotype. First, we use evolutionary epidemiology theory to clarify the interplay between demographic stochasticity and evolutionary dynamics to show that the
strategy always yields lower probability of evolutionary emergence. Second, we test experimentally these predictions with the introduction of bacteriophages into bacterial populations where we manipulated the diversity and the depth of immunity using a Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated (CRISPR-Cas) system. These biological assays confirm that pyramiding multiple defences into the same host genotype and avoiding combination with single-defence genotypes is a robust way to reduce pathogen evolutionary emergence. The experimental validation of these theoretical recommendations has practical implications in various areas, including for the optimal deployment of resistance varieties in agriculture and for the design of durable vaccination strategies.
Avian malaria has historically played an important role as a model in the study of human malaria, being a stimulus for the development of medical parasitology. Avian malaria has recently come back to ...the research scene as a unique animal model to understand the ecology and evolution of the disease, both in the field and in the laboratory. Avian malaria is highly prevalent in birds and mosquitoes around the world and is amenable to laboratory experimentation at each stage of the parasite's life cycle. Here, we take stock of 5 years of experimental laboratory research carried out using Plasmodium relictum SGS1, the most prevalent avian malaria lineage in Europe, and its natural vector, the mosquito Culex pipiens. For this purpose, we compile and analyse data obtained in our laboratory in 14 different experiments. We provide statistical relationships between different infection-related parameters, including parasitaemia, gametocytaemia, host morbidity (anaemia) and transmission rates to mosquitoes. This analysis provides a wide-ranging picture of the within-host and between-host parameters that may bear on malaria transmission and epidemiology.
Avian malaria parasites are prevalent around the world and infect a wide diversity of bird species. Here, we report the sequencing and analysis of high-quality draft genome sequences for two avian ...malaria species,
and
We identify 50 genes that are specific to avian malaria, located in an otherwise conserved core of the genome that shares gene synteny with all other sequenced malaria genomes. Phylogenetic analysis suggests that the avian malaria species form an outgroup to the mammalian
species, and using amino acid divergence between species, we estimate the avian- and mammalian-infective lineages diverged in the order of 10 million years ago. Consistent with their phylogenetic position, we identify orthologs of genes that had previously appeared to be restricted to the clades of parasites containing
and
, the species with the greatest impact on human health. From these orthologs, we explore differential diversifying selection across the genus and show that the avian lineage is remarkable in the extent to which invasion-related genes are evolving. The subtelomeres of the
and
genomes contain several novel gene families, including an expanded
multigene family. We also identify an expansion of reticulocyte binding protein homologs in
, and within these proteins, we detect distinct regions that are specific to nonhuman primate, humans, rodent, and avian hosts. For the first time in the
lineage, we find evidence of transposable elements, including several hundred fragments of LTR-retrotransposons in both species and an apparently complete LTR-retrotransposon in the genome of
.
Understanding how parental distance affects offspring fitness, i.e., the effects of inbreeding and outbreeding in natural populations, is a major goal in evolutionary biology. While inbreeding is ...often associated with fitness reduction (inbreeding depression), interpopulation outcrossing may have either positive (heterosis) or negative (outbreeding depression) effects. Within a metapopulation, all phenomena may occur with various intensities depending on the focal population (especially its effective size) and the trait studied. However, little is known about interpopulation variation at this scale. We here examine variation in inbreeding depression, heterosis, and outbreeding depression on life-history traits across a full-life cycle, within a metapopulation of the hermaphroditic snail Physa acuta. We show that all three phenomena can co-occur at this scale, although they are not always expressed on the same traits. A large variation in inbreeding depression, heterosis, and outbreeding depression is observed among local populations. We provide evidence that, as expected from theory, small and isolated populations enjoy higher heterosis upon outcrossing than do large, open populations. These results emphasize the need for an integrated theory accounting for the effects of both deleterious mutations and genetic incompatibilities within metapopulations and to take into account the variability of the focal population to understand the genetic consequences of inbreeding and outbreeding at this scale.
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