The implications of immunopathology for parasite evolution

By definition, parasites harm their hosts, but in many infections much of the pathology is driven by the host immune response rather than through direct damage inflicted by parasites. While these immunopathological effects are often well studied and understood mechanistically in individual disease interactions, there remains relatively little understanding of their broader impact on the evolution of parasites and their hosts. Here, we theoretically investigate the implications of immunopathology, broadly defined as additional mortality associated with the host's immune response, on parasite evolution. In particular, we examine how immunopathology acting on different epidemiological traits (namely transmission, virulence and recovery) affects the evolution of disease severity. When immunopathology is costly to parasites, such that it reduces their fitness, for example by decreasing transmission, there is always selection for increased disease severity. However, we highlight a number of host-parasite interactions where the parasite may benefit from immunopathology, and highlight scenarios that may lead to the evolution of slower growing parasites and potentially reduced disease severity. Importantly, we find that conclusions on disease severity are highly dependent on how severity is measured. Finally, we discuss the effect of treatments used to combat disease symptoms caused by immunopathology.     

How parasite interaction strategies alter virulence evolution in multi‐parasite communities

The majority of organisms host multiple parasite species, each of which can interact with hosts and competitors through a diverse range of direct and indirect mechanisms. These within‐host interactions can directly alter the mortality rate of coinfected hosts and alter the evolution of virulence (parasite‐induced host mortality). Yet we still know little about how within‐host interactions affect the evolution of parasite virulence in multi‐parasite communities. Here, we modeled the virulence evolution of two coinfecting parasites in a host population in which parasites interacted through cross immunity, immune suppression, immunopathology, or spite. We show (1) that these within‐host interactions have different effects on virulence evolution when all parasites interact with each other in the same way versus when coinfecting parasites have unique interaction strategies, (2) that these interactions cause the evolution of lower virulence in some hosts, and higher virulence in other hosts, depending on the hosts infection status, and (3) that for cross immunity and spite, whether parasites increase or decrease the evolutionarily stable virulence in coinfected hosts depended on interaction strength. These results improve our understanding of virulence evolution in complex parasite communities, and show that virulence evolution must be understood at the community scale.     

Rodent sociality and parasite diversity

The risk of parasitism is considered to be a general cost of sociality and individuals living in larger groups are typically considered to be more likely to be infected with parasites. However, contradictory results have been reported for the relationship between group size and infection by directly transmitted parasites. We used independent contrasts to examine the relationship between an index of sociality in rodents and the diversity of their macroparasites (helminths and arthropods such as fleas, ticks, suckling lice and mesostigmatid mites). We found that the species richness of directly transmitted ectoparasites, but not endoparasites, decreased significantly with the level of rodent sociality. A greater homogeneity in the biotic environment (i.e. a reduced number of cohabiting host species) of the more social species may have reduced ectoparasites' diversity by impairing ectoparasites transmission and exchange. Our finding may also result from beneficial outcomes of social living that include behavioural defences, like allogrooming, and the increased avoidance of parasites through dilution effects.     

Infectivity of Neoaplectana carpocapsae and Heterorhabditis heliothidis to pupae of the parasite Apanteles militaris

The infectivity of Neoaplectana carpocapsae and Heterorhabditis heliothidis to Apanteles militaris, a gregarious parasite of the armyworm, was deterntined at 100. 1,000, 5,000, and 10,000 nematodes per petri dish. For both nematode species, the percentage of infected A. militaris within a cocoon cluster decreased as inoculum levels decreased. At the highest inoculum level, N. carpocapsae infected an average of 32% of the parasite pupae within a cocoon cluster, whereas H. heliothidis infected an average of 22%. Covariance analysis indicated, however, that N. carpocapsae had significantly greater infectivity than did H. heliothidis. Some of the dauer juveniles of N. carpocapsae on the body of the armyworm contacted the emerging parasites and eventually became enveloped within the silken cocoons. Dauer juveniles produced by N. carpocapsae in parasite pupae could not penetrate and escape from silken cocoons even when the cocoons were placed in a moist environment.     

Metabarcoding of eukaryotic parasite communities describes diverse parasite assemblages spanning the primate phylogeny

Despite their ubiquity, in most cases little is known about the impact of eukaryotic parasites on their mammalian hosts. Comparative approaches provide a powerful method to investigate the impact of parasites on host ecology and evolution, though two issues are critical for such efforts: controlling for variation in methods of identifying parasites and incorporating heterogeneity in sampling effort across host species. To address these issues, there is a need for standardized methods to catalogue eukaryotic parasite diversity across broad phylogenetic host ranges. We demonstrate the feasibility of a metabarcoding approach for describing parasite communities by analysing faecal samples from 11 nonhuman primate species representing divergent lineages of the primate phylogeny and the full range of sampling effort (i.e. from no parasites reported in the literature to the best‐studied primates). We detected a number of parasite families and regardless of prior sampling effort, metabarcoding of only ten faecal samples identified parasite families previously undescribed in each host (x? = 8.5 new families per species). We found more overlap between parasite families detected with metabarcoding and published literature when more research effort—measured as the number of publications—had been conducted on the host species' parasites. More closely related primates and those from the same continent had more similar parasite communities, highlighting the biological relevance of sampling even a small number of hosts. Collectively, results demonstrate that metabarcoding methods are sensitive and powerful enough to standardize studies of eukaryotic parasite communities across host species, providing essential new tools for macroecological studies of parasitism.     

Latitudinal gradients of parasite species richness in primates

Infectious disease risk is thought to increase in the tropics, but little is known about latitudinal gradients of parasite diversity. We used a comparative data set encompassing 330 parasite species reported from 119 primate hosts to examine latitudinal gradients in the diversity of micro and macroparasites per primate host species. Analyses conducted with and without controlling for host phylogeny showed that parasite species richness increased closer to the equator for protozoan parasites, but not for viruses or helminths. Relative to other major parasite groups, protozoa reported from wild primates were transmitted disproportionately by arthropod vectors. Within the protozoa, our results revealed that vector‐borne parasites showed a highly significant latitudinal gradient in species richness. This higher diversity of vector‐borne protozoa near the tropics could be influenced by a greater abundance or diversity of biting arthropods in the tropics, or by climatic effects on vector behaviour and parasite development. Many vector‐borne diseases, such as leishmaniasis, trypanosomiasis, and malaria pose risks to both humans and wildlife, and nearly one‐third of the protozoan parasites from free‐living primates in our data set have been reported to infect humans. Because the geographical distribution and prevalence of many vector‐borne parasites are expected to increase because of global warming, these results are important for predicting future parasite‐mediated threats to biodiversity and human health.     

Effects of the swimbladder parasite Anguillicola crassus on the migration of European silver eels Anguilla anguilla in the Baltic Sea

In a mark–recapture study in 2006, migrating European Anguilla anguilla silver eels were caught, tagged and released in the Baltic Sea and recaptures in commercial pound nets examined for possible effects on migration of infection with the swimbladder parasite Anguillicola crassus . The overall recapture rate was 36%. The prevalence of infection was lowest at the northernmost sampling site. There were no significant differences between infected and uninfected A. anguilla in condition indices, body fat content and estimated migration speeds. Parasite infection intensity levels were significantly negatively correlated with times and distances covered between release and recapture, but did not correlate with migration speed. It appears that more heavily infected A. anguilla were relatively more vulnerable to recapture in pound nets. It is hypothesized that parasite-induced damage to the swimbladder inhibited vertical migrations and infected A. anguilla tended to migrate in shallower coastal waters, relatively close to the shore.     

Helminth parasite richness among vertebrates

The numbers of intestinal helminth species (parasite richnesS) recorded from each of 488 vertebrate host species are compared using data compiled from the published literature. Associations between parasite richness, sampling effort, host size and host habitat (aquatic versus terrestrial) are assessed using a method designed to control for phylogenetic association. Parasite richness increases with the number of surveys on which each estimate of parasite richness is based (sampling effort). When the effects of sampling effort are controlled for, there remains a strong positive relationship between parasite richness and host body size. There is no tendency for aquatic hosts to harbour more parasite species than terrestrial hosts independently of differences in sampling effort and body size. The results are interpreted in the context of hosts representing habitats for parasite colonization, resource allocation between parasite species, and the age of the major mammalian radiations.     

Helminth parasite diversity discloses age and sex differences in the foraging behaviour of southern lapwings (Vanellus chilensis)

Parasites with heteroxen cycles are important sources of information on the trophic relations of hosts. This is particularly instructive for species whose age‐based or sex‐based differences are hardly detected by behavioural observations. Here, we describe the helminth community of the omnivorous southern lapwing (Vanellus chilensis) and evaluate whether it is affected by the host's sex, age and body size. The species is sexually monomorphic in body length, but males are slightly heavier than females. We analysed 112 individuals collected in Curitiba, Brazil, in March 2010. All hosts were parasitized. The helminth community was composed of 10 species (the digeneans Leucochloridium parcum and Athesmia sp., the cestode Infula macrophallus, the acantocephalans Plagiorhynchus sp., Centrorhynchus sp., Mediorhynchus sp., and an unidentified Gigantorhynchida, and the nematodes Heterakis psophiae, Dispharynx nasuta and an unidentified Capillariidae), seven of which were novel reports for this host species. Prevalence ranged from <1% to 99%. Whereas I. macrophallus was the most prevalent species, D. nasuta showed the highest mean intensity and abundance of infection. The former was found in most hosts as single male–female pairs, suggesting the occurrence of intrasexual competition. The infracommunities of juvenile birds showed a higher parasite species richness than those of adult males and females, suggesting the exploitation of a wider array of prey. However, the three classes harboured seven parasite species. Differences in parasite diversity (lower in juveniles, intermediate in adult males and higher in adult females) reflect the evenness in the distribution of parasite specimens among taxa in each age–sex class and are compatible with differences in their foraging strategy. Finally, we conclude based on the cycles of the heteroxen species that southern lapwings preyed upon molluscs, coleopterans, woodlice and earthworms.     

Synthetic propeptide inhibits mosquito midgut chitinase and blocks sporogonic development of malaria parasite

Incessant transmission of the parasite by mosquitoes makes most attempts to control malaria fail. Blocking of parasite transmission by mosquitoes therefore is a rational strategy to combat the disease. Upon ingestion of blood meal mosquitoes secrete chitinase into the midgut. This mosquito chitinase is a zymogen which is activated by the removal of a propeptide from the N-terminal. Since the midgut peritrophic matrix acts as a physical barrier, the activated chitinase is likely to contribute to the further development of the malaria parasite in the mosquito. Earlier it has been shown that inhibiting chitinase activity in the mosquito midgut blocked sporogonic development of the malaria parasite. Since synthetic propeptides of several zymogens have been found to be potent inhibitors of their respective enzymes, we tested propeptide of mosquito midgut chitinase as an inhibitor and found that the propeptide almost completely inhibited the recombinant or purified native Anopheles gambiae chitinase. We also examined the effect of the inhibitory peptide on malaria parasite development. The result showed that the synthetic propeptide blocked the development of human malaria parasite Plasmodium falciparum in the African malaria vector An. gambiae and avian malaria parasite Plasmodium gallinaceum in Aedes aegypti mosquitoes. This study implies that the expression of inhibitory mosquito midgut chitinase propeptide in response to blood meal may alter the mosquito's vectorial capacity. This may lead to developing novel strategies for controlling the spread of malaria.     

Biology of parasite populations: population dynamics of bothriocephalids (Cestoda-Pseudophyllidea) in teleostean fish

Relationships between sympatric populations of four species of Cestoda belonging to the genus Bothriocephalus ( B. barbarus. B. gregarius, B. funiculus and B. scorpii ) and populations of their respective hosts Scophthalmus rhombus, Pserra maxima, Ciliata mustela and Myoxocephalus scorpius were investigated. The parasites were overdispersed within their host populations. The mean intensities of B. burbarus were 1.59 ( s.d. =0.83) in the Mediterranean (Gulf of Lions) and 1.25 ( s.d. =0.53) in the Atlantic (coasts of Brittany). The mean intensities of B. gregarius were 62.3 ( s.d. =49.7) in the Mediterranean and 14.06 ( s.d. =18.48) in the Atlantic, compared to 1.78 ( s.d. =0.3) for B. funiculus and 21.6 ( s.d. =17.3) for B. scorpii .
The distribution of prevalence of B. gregarius corresponded to a lognormal distribution while those of B. barbatus and B. fwticulus corresponded to negative binomials. No differences in infection could be related to host sex. The parasitization of B. gregariusdepended on host size. In brill, infection by E. barbatus was independent of host size and remained stable after the fish reached 180mm in length. Parasitization of turbot by E. gregarius was lower in young fish (≤110–150 mm) and increased with the host size. Compared to the Atlantic populations of B. gregarius and B. barbatus, the Mediterranean populations were more frequently and intensively infected. The differences in the population dynamics of B. gregarius and B. barbarus would appear to depend on whether or not the life cycle involves a paratenic host.     

Diet quality determines interspecific parasite interactions in host populations

The widespread occurrence of multiple infections and the often vast range of nutritional resources for their hosts allow that interspecific parasite interactions in natural host populations might be determined by host diet quality. Nevertheless, the role of diet quality with respect to multispecies parasite interactions on host population level is not clear. We here tested the effect of host population diet quality on the parasite community in an experimental study using Daphnia populations. We studied the effect of diet quality on Daphnia population demography and the interactions in multispecies parasite infections of this freshwater crustacean host. The results of our experiment show that the fitness of a low‐virulent microsporidian parasite decreased in low, but not in high‐host‐diet quality conditions. Interestingly, infections with the microsporidium protected Daphnia populations against a more virulent bacterial parasite. The observed interspecific parasite interactions are discussed with respect to the role of diet quality‐dependent changes in host fecundity. This study reflects that exploitation competition in multispecies parasite infections is environmentally dependent, more in particular it shows that diet quality affects interspecific parasite competition within a single host and that this can be mediated by host population‐level effects.     

Role of parasite transmission in promoting inbreeding: I. Infection intensities drive individual parasite selfing rates

Among parasitic organisms, inbreeding has been implicated as a potential driver of host–parasite co‐evolution, drug‐resistance evolution and parasite diversification. Yet, fundamental topics about how parasite life histories impact inbreeding remain to be addressed. In particular, there are no direct selfing‐rate estimates for hermaphroditic parasites in nature. Our objectives were to elucidate the mating system of a parasitic flatworm in nature and to understand how aspects of parasite transmission could influence the selfing rates of individual parasites. If there is random mating within hosts, the selfing rates of individual parasites would be an inverse power function of their infection intensities. We tested whether selfing rates deviated from within‐host random mating expectations with the tapeworm Oochoristica javaensis. In doing so, we generated, for the first time in nature, individual selfing‐rate estimates of a hermaphroditic flatworm parasite. There was a mixed‐mating system where tapeworms self‐mated more than expected with random mating. Nevertheless, individual selfing rates still had a significant inverse power relationship to infection intensities. The significance of this finding is that the distribution of parasite infection intensities among hosts, an emergent property of the transmission process, can be a key driver in shaping the primary mating system, and hence the level of inbreeding in the parasite population. Moreover, we demonstrated how potential population selfing rates can be estimated using the predicted relationship of individual selfing rates to intensities and showed how the distribution of parasites among hosts can indirectly influence the primary mating system when there is density‐dependent fecundity.     

Host modulation of parasite competition in multiple infections

Parasite diversity is a constant challenge to host immune systems and has important clinical implications, but factors underpinning its emergence and maintenance are still poorly understood. Hosts typically harbour multiple parasite genotypes that share both host resources and immune responses. Parasite diversity is thus shaped not only by resource competition between co-infecting parasites but also by host-driven immune-mediated competition. We investigated these effects in an insect-trypanosome system, combining in vivo and in vitro single and double inoculations. In vivo, a non-pathogenic, general immune challenge was used to manipulate host immune condition and resulted in a reduced ability of hosts to defend against a subsequent exposure to the trypanosome parasites, illustrating the costs of immune activation. The associated increase in available host space benefited the weaker parasite strains of each pair as much as the otherwise more competitive strains, resulting in more frequent multiple infections in immune-challenged hosts. In vitro assays showed that in the absence of a host, overall parasite diversity was minimal because the outcome of competition was virtually fixed and resulted in strain extinction. Altogether, this shows that parasite competition is largely host-mediated and suggests a role for host immune condition in the maintenance of parasite diversity.     

The social parasite wasp Polistes atrimandibularis does not form host races

Parasites that exploit the parental behaviour of several host species may be selected to form distinct host-specific genetic lineages. This process is well documented in bird brood parasites, but not in insect social parasites. Polistes atrimandibularis is the only paper-wasp social parasite known to exploit four host species. It does not form genetically distinct host races according to analyses based on microsatellite loci. Also, there were no size-matching between parasites and host species. Instead, P. atrimandibularis queens seemed to be successful as parasites in this population only when they originated from nests of P. dominulus, the largest species. The other host species are a sink for P. atrimandibularis since adult females emerging from those nests appear too small to usurp colonies themselves. Traits that may help P. atrimandibularis infiltrate multiple species may include its nonaggressive usurpation tactics and its ability to acquire host cuticular hydrocarbon recognition labels.     

No effect of host–parasite co‐evolution on host range expansion

Antagonistic co‐evolution between hosts and parasites (reciprocal selection for resistance and infectivity) is hypothesized to play an important role in host range expansion by selecting for novel infectivity alleles, but tests are lacking. Here, we determine whether experimental co‐evolution between a bacterium (Pseudomonas fluorescens SBW25) and a phage (SBW25Φ2) affects interstrain host range: the ability to infect different strains of P. fluorescens other than SBW25. We identified and tested a genetically and phenotypically diverse suite of co‐evolved phage variants of SBW25Φ2 against both sympatric and allopatric co‐evolving hosts (P. fluorescens SBW25) and a large set of other P. fluorescens strains. Although all co‐evolved phage had a greater host range than the ancestral phage and could differentially infect co‐evolved variants of P. fluorescens SBW25, none could infect any of the alternative P. fluorescens strains. Thus, parasite generalism at one genetic scale does not appear to affect generalism at other scales, suggesting fundamental genetic constraints on parasite adaptation for this virus.     

Coevolution of parasite virulence and host life history

Most models about the evolutionary interactions between a parasite's virulence and its host's life history neglect two potentially important aspects: epidemiological and coevolutionary feedback. We emphasize their importance by presenting models that describe the coevolution of a semelparous host's age at reproduction and a parasite's virulence in different environmental conditions. In particular, we first show that an epidemiological feedback will lead to a nonmonotonic response of the host's age at reproduction as virulence increases. We then show that the coevolutionary pressure on virulence can lead to complex associations between the host's life history and the parasite's virulence, which would not be expected with more traditional models of host or parasite evolution. Thus, for example, a high mortality rate of the host favours avirulent parasites and late reproduction of the host when the environmental conditions allow the host to grow rapidly, but early reproduction and high virulence when growth is slow.