Order and timing of infection with different parasite life stages impacts host and parasite life histories.

Co-exposure to multiple parasites can alter parasite success and host life history when compared to single infections. These infection outcomes can be affected by the order of parasite arrival, the host immune response, and the interspecific interactions among co-infecting parasites. In this study, we examined how the arrival order of two trematode parasites, Schistosoma mansoni and Echinostoma caproni, influenced parasite ecology and the life history of their snail host, Biomphalaria glabrata. Snail hosts were exposed to E. caproni cercariae before, with, and after their exposure to S. mansoni miracidia. We then measured the effects of this timing on infection prevalence, infection intensity of E. caproni metacercariae, and cercarial output of S. mansoni, as well as on snail reproduction and survival. Snails infected only with S. mansoni and snails exposed to E. caproni after S. mansoni both shed more cercariae than simultaneously exposed snails. Additionally, S. mansoni prevalence was lower in snails that were first exposed to E. caproni compared to snails that were exposed to E. caproni after S. mansoni. Moreover, snails exposed to E. caproni before S. mansoni did not differ in their survival compared to control snails, whereas simultaneously exposed snails and snails exposed to E. caproni after S. mansoni had lower survival than control snails. Combined, this prevalence and survival data suggest a potential protective role of early E. caproni exposure. The timing of E. caproni exposure impacts S. mansoni establishment and reproduction, but host survival patterns are likely driven by S. mansoni prevalence alone.

Host preference of field-derived Schistosoma mansoni is influenced by snail host compatibility and infection status.

Schistosome parasites cause a chronic inflammatory disease in humans, and recent studies have emphasized the importance of control programs for understanding the aquatic phases of schistosomiasis transmission. The host-seeking behavior of larval schistosomes (miracidia) for their snail intermediate hosts plays a critical role in parasite transmission. Using field-derived strains of Kenyan snails and parasites, we tested two main hypotheses: (1) Parasites prefer the most compatible host, and (2) parasites avoid hosts that are already infected. We tested preference to three Biomphalaria host snail taxa (B. pfeifferi, B. sudanica, and B. choanomphala), using allopatric and sympatric Schistosoma mansoni isolates and two different nonhost snail species that co-occur with Biomphalaria, Bulinus globosus, and Physa acuta. We also tested whether schistosomes avoid snail hosts that are already infected by another trematode species and whether competitive dominance played a role in their behavior. Preference was assessed using two-way choice chambers and by visually counting parasites that moved toward competing stimuli. In pairwise comparisons, we found that S. mansoni did not always prefer the more compatible snail taxon, but never favored an incompatible host over a compatible host. While parasites preferred B. pfeifferi to the nonhost species B. globosus, they did not significantly prefer B. pfeifferi versus P. acuta, an introduced species in Kenya. Finally, we demonstrated that parasites avoid infected snails if the resident parasite was competitively dominant (Patagifer sp.), and preferred snails infected with subordinates (xiphidiocercariae) to uninfected snails. These results provide evidence of "fine tuning" in the ability of schistosome miracidia to detect hosts; however, they did not always select hosts that would maximize fitness. Appreciating such discriminatory abilities could lead to a better understanding of how ecosystem host and parasite diversity influences disease transmission and could provide novel control mechanisms to improve human health.

Correction: Opportunity or catastrophe? effect of sea salt on host-parasite survival and reproduction.

[This corrects the article DOI: 10.1371/journal.pntd.0009524.].

Opportunity or catastrophe? effect of sea salt on host-parasite survival and reproduction.

Seawater intrusion associated with decreasing groundwater levels and rising seawater levels may affect freshwater species and their parasites. While brackish water certainly impacts freshwater systems globally, its impact on disease transmission is largely unknown. This study examined the effect of artificial seawater on host-parasite interactions using a freshwater snail host, Biomphalaria alexandrina, and the human trematode parasite Schistosoma mansoni. To evaluate the impact of increasing salinity on disease transmission four variables were analyzed: snail survival, snail reproduction, infection prevalence, and the survival of the parasite infective stage (cercariae). We found a decrease in snail survival, snail egg mass production, and snail infection prevalence as salinity increases. However, cercarial survival peaked at an intermediate salinity value. Our results suggest that seawater intrusion into freshwaters has the potential to decrease schistosome transmission to humans.

The Road Not Taken: Host Infection Status Influences Parasite Host-Choice.

The manipulation of host organisms by their parasites has captured the attention of ecologists, parasitologists, and the public. However, our knowledge of parasite behavior independent of a host is limited despite the far-reaching implications of parasite behavior. Parasite behaviors can help explain trematode community structure, the aggregation of parasites within host populations, and can potentially be harnessed in biocontrol measures. In this study, we used a simple choice chamber design to examine whether trematode parasites can detect the infection status of a potential host and avoid hosts infected with a competitively dominant species. Our results show that Schistosoma mansoni, a competitively subordinate species, can detect and avoid hosts infected with a competitively dominant parasite, Echinostoma caproni. However, E. caproni, despite showing a significant preference for snails infected with S. mansoni over uninfected snails, showed little ability to detect the infection status of the host or even the host's presence. We propose subordinate species may be under stronger selection to avoid dominant competitors whereas dominant competitors may be more strongly selected to find any suitable host, regardless of infection status. Previous research has focused on parasites distinguishing between 'host' and 'non-host', which does not fully capture the complexity of these interactions. However, the ability of subordinate parasites to determine the infection status of a host results in a consistent evolutionary advantage.

Parasites and Their Impact on Ecosystem Nutrient Cycling.

Consumer species alter nutrient cycling through nutrient transformation, transfer, and bioturbation. Parasites have rarely been considered in this framework despite their ability to indirectly alter the cycling of nutrients via their hosts. A simple mathematical framework can be used to assess the relative importance of parasite-derived nutrients in an ecosystem.

One stimulus-Two responses: Host and parasite life-history variation in response to environmental stress.

Climate change stressors will place different selective pressures on both parasites and their hosts, forcing individuals to modify their life-history strategies and altering the distribution and prevalence of disease. Few studies have investigated whether parasites are able to respond to host stress and respond by varying their reproductive schedules. Additionally, multiple environmental stressors can limit the ability of a host to respond adaptively to parasite infection. This study compared both host and parasite life-history parameters in unstressed and drought-stressed environments using the human parasite, Schistosoma mansoni, in its freshwater snail intermediate host. Snail hosts infected with the parasite demonstrated a significant reproductive burst during the prepatent period (fecundity compensation), but that response was absent in a drought-stressed environment. This is the first report of the elimination of host fecundity compensation to parasitism when exposed to additional environmental stress. More surprisingly, we found that infections in drought-stressed snails had significantly higher parasite reproductive outputs than infections in unstressed snails. The finding suggests that climate change may alter the infection dynamics of this human parasite.

The influence of trematode parasite burden on gene expression in a mammalian host.

BACKGROUND: Parasites can profoundly impact their hosts and are responsible for a plethora of debilitating diseases. To identify global changes in host gene expression related to parasite infection, we sequenced, assembled, and annotated the liver transcriptomes of Balb/cj mice infected with the trematode parasite Schistosoma mansoni and compared the results to uninfected mice. We used two different methodologies (i.e. de novo and reference guided) to evaluate the influence of parasite sequences on host transcriptome assembly. RESULTS: Our results demonstrate that the choice of assembly methodology significantly impacted the proportion of parasitic reads detected from the host library, yet the presence of non-target (xenobiotic) sequences did not create significant structural errors in the assembly. After removing parasite sequences from the mouse transcriptomes, we analyzed host gene expression under different parasite infection levels and observed significant differences in the associated immunologic and metabolic responses based on infection level. In particular, genes associated with T-helper type 1 (Th-1) and T-helper type 2 (Th-2) were up-regulated in infected mice whereas genes related to amino acid and carbohydrate metabolism were down-regulated in infected mice. These changes in gene expression scale with infection status and likely impact the evolutionary fitness of hosts. CONCLUSIONS: Overall, our data indicate that a) infected mice reduce the expression of key metabolic genes in direct proportion to their infection level; b) infected mice similarly increase the expression of key immune genes in response to infection; c) patterns of gene expression correspond to the pathological symptoms of schistosomiasis; and d) identifying and filtering out non-target sequences (xenobiotics) improves differential expression prediction. Our findings identify parasite targets for RNAi or other therapies and provide a better understanding of the pathology and host immune repertoire involved in response to S. mansoni infections.

Horizontal gene transfer in schistosomes: A critical assessment.

Horizontal gene transfer (HGT), the movement of genetic material between distinct evolutionary lineages, has long been known as a principal force of diversification and adaptation of prokaryotes. More recently, genomic and transcriptomic datasets have suggested gene transfers among various eukaryotic taxa (e.g., Porifera, Cnidaria, Nematoda, Arthropoda, Rotifera, Craniata, and Plantae). Although the exact mechanism of eukaryotic HGT is often unknown, host-parasite interactions may provide ample opportunities for HGT. Schistosomes are trematode blood parasites with complex life cycles that have been repeatedly implicated in HGT. We employed molecular, bioinformatic and phylogenetic approaches to critically analyze 13 published reports of direct HGTs between schistosomes and their hosts to better understand host-parasite co-evolution. Our research suggests that reported cases of schistosome-associated HGT may be due to technical artifacts as opposed to biological reality as we were unable to substantiate them. HGT clearly occurs in eukaryotic organisms, but the burden of proof is high and we emphasize the importance of multiple lines of evidence to conclusively document HGT.

The genomic proliferation of transposable elements in colonizing populations: Schistosoma mansoni in the new world.

Transposable elements (TEs) are mobile genes with an inherent ability to move within and among genomes. Theory predicts that TEs proliferate extensively during physiological stress due to the breakdown of TE repression systems. We tested this hypothesis in Schistosoma mansoni, a widespread trematode parasite that causes the human disease schistosomiasis. According to phylogenetic analysis, S. mansoni invaded the new world during the last 500 years. We hypothesized that new world strains of S. mansoni would have more copies of TEs than old world strains due to the physiological stress associated with invasion of the new world. We quantified the copy number of six TEs (Saci-1, Saci-2 and Saci-3, Perere-1, Merlin-sm1, and SmTRC1) in the genome and the transcriptome of old world and new world strains of S. mansoni, using qPCR relative quantification. As predicted, the genomes of new world parasites contain significantly more copies of class I and class II TEs in both laboratory and field strains. However, such differences are not observed in the transcriptome suggesting that either TE silencing mechanisms have reactivated to control the expression of these elements or the presence of inactive truncated copies of TEs.

Can host ecology and kin selection predict parasite virulence?

Parasite virulence, or the damage a parasite does to its host, is measured in terms of both host costs (reductions in host growth, reproduction and survival) and parasite benefits (increased transmission and parasite numbers) in the literature. Much work has shown that ecological and genetic factors can be strong selective forces in virulence evolution. This review uses kin selection theory to explore how variations in host ecological parameters impact the genetic relatedness of parasite populations and thus virulence. We provide a broad overview of virulence and population genetics studies and then draw connections to existing knowledge about natural parasite populations. The impact of host movement (transporting parasites) and host resistance (filtering parasites) on the genetic structure and virulence of parasite populations is explored, and empirical studies of these factors using Plasmodium and trematode systems are proposed.

Elucidating the temporal and spatial dynamics of Biomphalaria glabrata genetic diversity in three Brazilian villages.

OBJECTIVE: The freshwater snail Biomphalaria glabrata is the principal intermediate host for the parasite Schistosoma mansoni within Brazil. We assessed the potential effects of snail population dynamics on parasite transmission dynamics via population genetics. METHODS: We sampled snail populations located within the confines of three schistosome-endemic villages in the state of Minas Gerais, Brazil. Snails were collected from individual microhabitats following seasonal periods of flood and drought over the span of 1 year. Snail spatio-temporal genetic diversity and population differentiation of 598 snails from 12 sites were assessed at seven microsatellite loci. RESULTS: Average genetic diversity was relatively low, ranging from 4.29 to 9.43 alleles per locus, and overall, subpopulations tended to exhibit heterozygote deficits. Genetic diversity was highly spatially partitioned among subpopulations, while virtually, no partitioning was observed across temporal sampling. Comparison with previously published parasite genetic diversity data indicated that S. mansoni populations are significantly more variable and less subdivided than those of the B. glabrata intermediate hosts. DISCUSSION: Within individual Brazilian villages, observed distributions of snail genetic diversity indicate temporal stability and very restricted gene flow. This is contrary to observations of schistosome genetic diversity over the same spatial scale, corroborating the expectation that parasite gene flow at the level of individual villages is likely driven by vertebrate host movement.

Hosts, parasites, and horizontal gene transfer.

Mendelian inheritance transfers genes vertically within lineages, whereas horizontal gene transfer (HGT) moves genetic material between or among lineages. Herein, we explore possible mechanisms of HGT between parasites and their hosts, as their intimate contact affords substantial opportunities for HGT. We review studies of host-parasite HGT, discussing their merits, their shortcomings, and the multiple lines of evidence needed to conclusively document HGT while avoiding false positives. We focus mainly on schistosomes and other parasites with complex life cycles as they provide numerous opportunities for HGT among the parasite, intermediate, and definitive host genomes. We also highlight future research directions that could prove illuminating with regard to the occurrence, prevalence, and overall importance of HGT in host-parasite coevolution.

Molecular assessment of trematode co-infection and intraspecific competition in molluscan intermediate hosts.

In natural populations of the human parasite Schistosoma mansoni, parasite distribution among snail intermediate hosts is generally overdispersed, such that a small proportion of hosts harbor the majority of parasite genotypes. Within these few infected snails, researchers have found that it can be common for hosts to harbor multiple parasite genotypes, creating circumstances in which co-infecting parasites are faced with potential competition over limited host resources. Much theoretical modeling has focused on parasite competition, especially regarding the influence of co-infection on parasite exploitation strategy evolution. However, particularly in the case of intra-molluscan intermediate stages, empirical investigations of parasite-parasite competition have often hinged on the untested assumption that co-exposure produces co-infection. That is, infected hosts exposed to multiple strains have been assumed to harbor multiple strains, regardless of the true nature of the infection outcome. Here we describe a real-time quantitative PCR method to distinguish the conditions of multiple- versus single-strain infection, as well as quantify the relative larval output of co-infecting strains. We applied the method to an empirical investigation of intraspecific parasite competition between S. mansoni strains within the intermediate snail host Biomphalaria glabrata, assessing co-exposure's effects on parasite infectivity and productivity and the concomitant effects on host fitness. Overall, there was no effect of parasite co-infection on snail life history traits relative to single-strain infection. Parasite infectivity significantly increased as a result of increasing overall miracidial dose, rather than co-exposure, though strain-specific productivity was significantly reduced in co-infections in manner consistent with resource competition. Moreover, we show that less than half of infected, co-exposed hosts had patent co-infections and demonstrate the utility of this molecular tool for the study of trematode life history variation in molluscan hosts.

Revealing cryptic parasite diversity in a definitive host: echinostomes in muskrats.

Many trematode groups have a long history of systematic revision, which can make parasite identification a difficult task. The trematode parasites of muskrats are no exception. Here, we highlight the systematic issues associated with trematodes of muskrats (Ondatra zibethicus). Then, we demonstrate the utility of using both morphological and molecular tools to identify these parasites. Morphological examinations of specimens from muskrats (n = 63) first suggested that at least 4 genera were present including Echinostoma, Wardius, Quinqueserialis, and Notocotylus. For the latter 3 groups, the 28S region verified this assessment. For echinostomes, ND1 sequences revealed at least 5 genetic lineages. A particular lineage, Echinostoma trivolvis lineage b, predominated in both prevalence and intensity of infection. Molecular sequences provided a more accurate estimate of echinostome diversity in the muskrats and further support the idea that E. trivolvis is a species complex. Future studies will focus on whether there are differences in host specificity among the E. trivolvis lineages. In addition, this study has provided initial sequences that will help verify the life cycles of Wardius, Quinqueserialis, and especially, Notocotylus. By linking molecular, morphological, and life history information, we can better understand parasite diversity.

Interactions among virulence, coinfection and drug resistance in a complex life-cycle parasite.

Motivated by relatively recent empirical studies on Schistosoma mansoni, we use a mathematical model to investigate the impacts of drug treatment of the definitive human host and coinfection of the intermediate snail host by multiple parasite strains on the evolution of parasites' drug resistance. Through the examination of evolutionarily stable strategies (ESS) of parasites, our study suggests that higher levels of drug treatment rates (which usually tend to promote monomorphism as the evolutionary equilibrium) favor parasite strains that have a higher level of drug resistance. Our study also shows that whether coinfection of intermediate hosts affects the levels of drug resistance at ESS points and their stability depends on the assumptions on the cost of parasites paid for drug resistance, coinfection functions and parasites' reproduction within coinfected hosts. This calls for more empirical studies on the parasite.

Evolution of host resistance to parasite infection in the snail-schistosome-human system.

The evolutionary strategies that emerge within populations can be dictated by numerous factors, including interactions with other species. In this paper, we explore the consequences of such a scenario using a host-parasite system of human concern. By analyzing the dynamical behaviors of a mathematical model we investigate the evolutionary outcomes resulting from interactions between Schistosoma mansoni and its snail and human hosts. The model includes two types of snail hosts representing resident and mutant types. Using this approach, we focus on establishing evolutionary stable strategies under conditions where snail hosts express different life-histories and when drug treatment is applied to an age-structured population of human hosts. Results from this work demonstrate that the evolutionary trajectories of host-parasite interactions can be varied, and at times, counter-intuitive, based on parasite virulence, host resistance, and drug treatment.

Transmission dynamics of two strains of Schistosoma mansoni utilizing novel intermediate and definitive hosts.

The intimate host-parasite relationship mandates adaptation to the genetic and phenotypic variability of their counterparts. Here, inbred and outcrossed strains of Schistosoma mansoni were challenged with "local" and "novel" intermediate and definitive hosts to examine effects of genetic variability and novelty on infection success and dynamics. Genetically distinct lines of Biomphalaria glabrata intermediate hosts exposed to inbred and outcrossed S. mansoni larvae were assessed for differences in both snail and parasite life-history parameters. Cercariae from each parasite-snail treatment were used to infect "local" and "novel" Mus musculus definitive hosts to assess parasite infectivity and fitness. Outcrossed parasites significantly reduced snail growth, were more productive, and induced greater host mortality than inbred parasites. Mouse strain did not influence parasite infectivity or reproduction, but parasite and snail host genetic background did, affecting both sex-specific infectivity and parasite productivity. Overall, genetic background of S. mansoni and its intermediate snail host altered life history traits and transmission dynamics of the parasite throughout its life cycle.