Behavior out of control: Experimental evolution of resistance to host manipulation

Many parasites alter their host's phenotype in a manner that enhances their own fitness beyond the benefits they would gain from normal exploitation. Such host manipulation is rarely consistent with the host's best interests resulting in suboptimal and often fatal behavior from the host's perspective. In this case, hosts should evolve resistance to host manipulation. The cestode Schistocephalus solidus manipulates the behavior of its first intermediate copepod host to reduce its predation susceptibility and avoid fatal premature predation before the parasite is ready for transmission to its subsequent host. Thereafter, S. solidus increases host activity to facilitate transmission. If successful, this host manipulation is necessarily fatal for the host. I selected the copepod Macrocyclops albidus, a first intermediate host of S. solidus, for resistance or susceptibility to host manipulation to investigate their evolvability. Selection on the host indeed increased host manipulation in susceptible and reduced host manipulation in resistant selection lines. Interestingly, this seemed to be at least partly due to changes in the baseline levels of the modified trait (activity) rather than actual changes in resistance or susceptibility to host manipulation. Hence, hosts seem restricted in how rapidly and efficiently they can evolve resistance to host manipulation.     

The population biology of parasite-induced changes in host behavior

The ability of parasites to change the behavior of infected hosts has been documented and reviewed by a number of different authors (Holmes and Bethel, 1972; Moore, 1984a). This review attempts to quantify the population dynamic consequences of this behavior by developing simple mathematical models for the most frequently recorded of such parasite life cycles. Although changes in the behavior of infected hosts do occur for pathogens with direct life cycles, they are most commonly recorded in the intermediate hosts of parasites with complex life cycles. All the changes in host behavior serve to increase rates of transmission of the parasites between hosts. In the simplest case the changes in behavior increase rates of contact between infected and susceptible conspecific hosts, whereas in the more complex cases fairly sophisticated manipulations of the host's behavioral repertory are achieved. Three topics are dealt with in some detail: (1) the behavior of the insect vectors of such diseases as malaria and trypanosomiasis; (2) the intermediate hosts of helminths whose behavior is affected in such a way as to make them more susceptible to predation by the definitive host in the life cycle; and (3) the behavior and fecundity of molluscs infected with asexually reproducing parasitic flatworms. In each case an expression is derived for R0, the basic reproductive rate of the parasite when first introduced into the population. This is used to determine the threshold numbers of definitive and intermediate hosts needed to maintain a population of the pathogen. In all cases, parasite-induced changes in host behavior tend to increase R0 and reduce the threshold number of hosts required to sustain the infection. The population dynamics of the interaction between parasites and their hosts are then explored using phase plane analyses. This suggests that both the parasite and intermediate host populations may show oscillatory patterns of abundance. When the density of the latter is low, parasite-induced changes in host behavior increase this tendency to oscillate. When intermediate host population densities are high, parasite population density is determined principally by interactions between the parasites and their definitive hosts, and changes in the behavior of intermediate hosts are less important in determining parasite density. Analysis of these models also suggests that both asexual reproduction of the parasite within a host and parasite-induced reduction in host fecundity may be stabilizing mechanisms when they occur in the intermediate hosts of parasite species with indirect life cycles.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effects of parasite age and intensity on variability in acanthocephalan-induced behavioural manipulation

Numerous parasites with complex life cycles are able to manipulate the behaviour of their intermediate host in a way that increases their trophic transmission to the definitive host. Pomphorhynchus laevis, an acanthocephalan parasite, is known to reverse the phototactic behaviour of its amphipod intermediate host, Gammarus pulex, leading to an increased predation by fish hosts. However, levels of behavioural manipulation exhibited by naturally-infected gammarids are extremely variable, with some individuals being strongly manipulated whilst others are almost not affected by infection. To investigate parasite age and parasite intensity as potential sources of this variation, we carried out controlled experimental infections on gammarids using parasites from two different populations. We first determined that parasite intensity increased with exposure dose, but found no relationship between infection and host mortality. Repeated measures confirmed that the parasite alters host behaviour only when it reaches the cystacanth stage which is infective for the definitive host. They also revealed, we believe for the first time, that the older the cystacanth, the more it manipulates its host. The age of the parasite is therefore a major source of variation in parasite manipulation. The number of parasites within a host was also a source of variation. Manipulation was higher in hosts infected by two parasites than in singly infected ones, but above this intensity, manipulation did not increase. Since the development time of the parasite was also different according to parasite intensity (it was longer in doubly infected hosts than in singly infected ones, but did not increase more in multi-infected hosts), individual parasite fitness could depend on the compromise between development time and manipulation efficiency. Finally, the two parasite populations tested induced slightly different degrees of behavioural manipulation.     

Who is in control of the stickleback immune system: interactions between Schistocephalus solidus and its specific vertebrate host

The cestode Schistocephalus solidus is a frequent parasite of three-spined sticklebacks and has a large impact on its host's fitness. Selection pressure should therefore be high on stickleback defence mechanisms, like an efficient immune system, and also on parasite strategies to overcome these. Even though there are indications for manipulation of the immune system of its specific second intermediate host by the cestode, nothing is yet known about the chronology of specific interactions of S. solidus with the stickleback immune system. We here expected sticklebacks to first mount an innate immune response directly post-exposure to the parasite to clear the infection at an early stage and after an initial lag phase to upregulate adaptive immunity. Most interestingly, we did not find any upregulation of the specific lymphocyte-mediated immune response. Also, the pattern of activation of the innate immune system did not match our expectations: the proliferation of monocytes followed fluctuating kinetics suggesting that the parasite repeatedly installs a new surface coat not immunogenic to the host. Furthermore, the respiratory burst activity, which has the potential to clear an early S. solidus infection, was upregulated very late during infection, when the parasite was too big to be cleared but ready for transmission to its final host. We here suggest that the late activation of the innate immune system interferes with the neuroendocrine system, which mediates reduced predation avoidance behaviour and so facilitates the transmission to the final host.     

When trophically‐transmitted parasites combine predation enhancement with predation suppression to optimize their transmission

Trophically‐transmitted parasites are known for their ability to enhance predation of their intermediate host but they are less known for their ability to suppress predation. We review recent literature on host manipulation explaining why and when in its life cycle a parasite benefits from preventing the predation of its host. Predation suppression occurs in intermediate hosts as long as the parasite larva has not reached the developmental conditions allowing it to successfully establish in the next host (competency). We also examine the possibility that predation suppression may occur in hosts harbouring competent larvae (post competency) since some parasites have been shown to manipulate host behaviour in a way that decreases the risk of parasite death through non‐host predation (i.e. the consumption of its intermediate host by a predator that does not risk infection). Predation suppression when the parasite is competent has to be considered with respect to non‐host predation risk and is not mutually exclusive with predation enhancement. We use the recent theoretical advances in host manipulation to investigate the conditions under which predation suppression could evolve post competency.     

Host manipulation by parasites in the world of dead-end predators: adaptation to enhance transmission?

Trophically transmitted parasites often alter their intermediate host's phenotype, thereby predisposing the hosts to increased predation. This is generally considered a parasite strategy evolved to enhance transmission to the next hosts. However, the adaptive value of host manipulation is not clear as it may be associated with costs, such as increased susceptibility to predators that are unsuitable next hosts for the parasites. We examined the ratio between the benefits and costs of host manipulation for transmission success of Acanthocephalus lucii (Acanthocephala), a parasite that alters the hiding behaviour and pigmentation of its isopod hosts. We experimentally compared the susceptibility of infected and uninfected isopods to predation by perch (Perca fluvialis; definitive host of the parasite) and dragonfly larvae (dead end). We found that the parasite predisposed the isopods to predation by both predators. However, the increased predation vulnerability of the infected isopods was higher towards perch. This suggests that, despite the costs due to non-host predation, host manipulation may still be advantageous for the parasite.     

Protection first then facilitation: a manipulative parasite modulates the vulnerability to predation of its intermediate host according to its own developmental stage

Many trophically transmitted parasites with complex life cycles manipulate their intermediate host behavior in ways facilitating their transmission to final host by predation. This facilitation generally results from lowering host's antipredatory defenses when the parasite is infective to the final host. However, a recent theoretical model predicts that an optimal parasitic strategy would be to protect the intermediate host from predation when noninfective, before switching to facilitation when the infective stage is reached. We tested this hypothesis in the fish acanthocephalan parasite Pomphorhynchus laevis using the amphipod Gammarus pulex as intermediate host. Gammarids parasitized by noninfective stage of P. laevis (acanthella) hid significantly more under refuges than uninfected ones. In addition, acanthella-infected gammarids were less predated upon by trout than uninfected ones. As predicted, a switch toward decreased antipredatory behavior of G. pulex and enhanced vulnerability to predation was found when P. laevis reached the stage infective to its final host. The parasites appear to be able to exploit plasticity in host antipredatory responses, and shift the host optimal response toward their own optimal balance.     

Inter- and intraspecific conflicts between parasites over host manipulation

Host manipulation is a common strategy by which parasites alter the behaviour of their host to enhance their own fitness. In nature, hosts are usually infected by multiple parasites. This can result in a conflict over host manipulation. Studies of such a conflict in experimentally infected hosts are rare. The cestode Schistocephalus solidus (S) and the nematode Camallanus lacustris (C) use copepods as their first intermediate host. They need to grow for some time inside this host before they are infective and ready to be trophically transmitted to their subsequent fish host. Accordingly, not yet infective parasites manipulate to suppress predation. Infective ones manipulate to enhance predation. We experimentally infected laboratory-bred copepods in a manner that resulted in copepods harbouring (i) an infective C plus a not yet infective C or S, or (ii) an infective S plus a not yet infective C. An infective C completely sabotaged host manipulation by any not yet infective parasite. An infective S partially reduced host manipulation by a not yet infective C. We hence show experimentally that a parasite can reduce or even sabotage host manipulation exerted by a parasite from a different species.     

Evolution of complex life cycles in trophically transmitted helminths. II. How do life‐history stages adapt to their hosts?

We review how trophically transmitted helminths adapt to the special problems associated with successive hosts in complex cycles. In intermediate hosts, larvae typically show growth arrest at larval maturity (GALM). Theoretical models indicate that optimization of size at GALM requires larval mortality rate to increase with time between infection and GALM: low larval growth or paratenicity (no growth) arises from unfavourable growth and mortality rates in the intermediate host and low transmission rates to the definitive host. Reverse conditions favour high GALM size or continuous growth. Some support is found for these predictions. Intermediate host manipulation involves predation suppression (which decreases host vulnerability before the larva can establish in its next host) and predation enhancement (which increases host vulnerability after the larva can establish in its next host). Switches between suppression and enhancement suggest adaptive manipulation. Manipulation conflicts can occur between larvae of different ages/species a host individual. Larvae must usually develop to GALM before becoming infective to the next host, possibly due to trade‐offs, e.g. between growth/survival in the present host and infection ability for the next host. In definitive hosts, if mortality rate is constant, optimal growth before switching to reproduction is set by the growth/morality rate ratio. Rarely, no growth occurs in definitive hosts, predicted (with empirical support) when larval size on infection exceeds growth/mortality rate. Tissue migration patterns and residence sites may be explained by variations in growth/mortality rates between host gut and soma, migration costs and benefits of releasing eggs in the gut.     

Parasite-induced alteration of plastic response to predation threat: increased refuge use but lower food intake in Gammarus pulex infected with the acanothocephalan Pomphorhynchus laevis

Larvae of many trophically-transmitted parasites alter the behaviour of their intermediate host in ways that increase their probability of transmission to the next host in their life cycle. Before reaching a stage that is infective to the next host, parasite larvae may develop through several larval stages in the intermediate host that are not infective to the definitive host. Early predation at these stages results in parasite death, and it has recently been shown that non-infective larvae of some helminths decrease such risk by enhancing the anti-predator defences of the host, including decreased activity and increased sheltering. However, these behavioural changes may divert infected hosts from an optimal balance between survival and foraging (either seeking food or a mate). In this study, this hypothesis was tested using the intermediate host of the acanthocephalan parasite Pomphorhynchus laevis, the freshwater amphipod Gammarus pulex. We compared activity, refuge use, food foraging and food intake of hosts experimentally infected with the non-infective stage (acanthella), with that of uninfected gammarids. Behavioural assays were conducted in four situations varying in predation risk and in food accessibility. Acanthella-infected amphipods showed an increase in refuge use and a general reduction in activity and food intake. There was no effect of parasite intensity on these traits. Uninfected individuals showed plastic responses to water-borne cues from fish by adjusting refuge use, activity and food intake. They also foraged more when the food was placed outside the refuge. At the intra-individual level, refuge use and food intake were positively correlated in infected gammarids only. Overall, our findings suggest that uninfected gammarids exhibit risk-sensitive behaviour including increased food intake under predation risk, whereas gammarids infected with the non-infective larvae of P. laevis exhibit a lower motivation to feed, irrespective of predation risk and food accessibility.     

Host manipulation as a parasite transmission strategy when manipulation is exploited by non-host predators

Trophically transmitted parasites often alter their intermediate host's phenotype, thereby predisposing hosts to increased predation. This is generally considered to be a parasite strategy evolved to enhance transmission to the next host. However, the adaptive value of host manipulation is not clear, as it may be associated with costs, such as increased susceptibility to predator species that are unsuitable next hosts for the parasites. Thus, it has been proposed that, to be adaptive, manipulation should be specific by predisposing hosts more strongly to predation by target hosts (next host in the life cycle) than to non-hosts. Here we formally evaluate this prediction, and show that manipulation does not have to be specific to be adaptive. However, when manipulation is nonspecific, it needs to effectively increase the overall predation risk of infected hosts if it is to increase the parasite transmission probability. Thus, when initial predation risk is low, even highly nonspecific manipulation strategies can be adaptive. However, when initial predation risk is high, manipulation needs to be more specific to increase parasite transmission success. Therefore, nonspecific host manipulation may evolve in nature, but the adaptive value of a certain manipulation strategy can vary among different parasite populations depending on the variation in initial predation risk.     

Two different strategies of host manipulation allow parasites to persist in intermediate–definitive host systems

Trophically transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate–definitive host systems, two strategies of host manipulation have been evolved: increasing the rate of transmission to the definitive host by increasing the chance that the definitive host will prey on the intermediate host, or increasing the lifespan of the parasite in the intermediate host by decreasing the predation chance when the intermediate host is not yet infectious. As the second strategy is less well studied than the first, it is unknown under what conditions each of these strategies is prevailed and evolved. We analysed the effect of both strategies on the presence of parasites in intermediate–definitive host systems with a structured population model. We show that the parasite can increase the parameter space where it can persist in the intermediate–definitive host system using one of these two strategies of host manipulation. We found that when the intermediate host or the definitive host has life‐history traits that allow the definitive host to reach large population densities, that is high reproduction rate of the intermediate host or high conversion efficiency of the definitive host (efficiency at which the uninfected definitive host converts caught intermediate hosts into offspring), respectively, evolving manipulation to decrease the predation chance of the intermediate host will be more beneficial than manipulation to increase the predation chance to enhance transmission. Furthermore, manipulation to decrease the predation chance of the intermediate host results in higher population densities of infected intermediate hosts than manipulation that increases the predation chance to enhance transmission. Our study shows that host manipulation in early stages of the parasite development to decrease predation might be a more frequently evolved way of host manipulation than is currently assumed.     

Testing alternative hypotheses for variation in amphipod behaviour and life history in relation to parasitism.

We tested two hypotheses concerning changes in investment in current reproduction for parasitised hosts, using amphipods (Corophium volutator) which act as second intermediate hosts for trematodes (Gynaecoyla aduncta). One hypothesis requires that parasites exert control over their hosts (parasite manipulation), whereas the other predicts that hosts control decisions over investment (adaptive host response). Although these hypotheses are viewed as mutually exclusive, our various results support both hypotheses. For example, female amphipods infected by late-stage larvae were often found crawling at times when predation by sandpipers (Calidris pusilla), which are the final hosts for trematodes, was likely, while uninfected females typically remained in their burrows. Furthermore, old females that were newly-infected by trematodes often aborted and ate their young. Both of these responses seem inconsistent with female investment in current reproduction, but can be interpreted as adaptive parasite manipulation. In contrast, young non-ovigerous females that were newly-infected hastened the onset of their parturial moult and thus, time to becoming receptive. This response can be explained as a host adaptation to minimise the cost of parasites. We contend that differences between parasitised and unparasitised hosts in behaviour or investment can be explained as both parasite and host adaptations, expressed at different times in the host's life history. Such compromise will help explain the persistence of parasite-host associations in nature.     

Priority effects within coinfected hosts can drive unexpected population‐scale patterns of parasite prevalence

Organisms are frequently coinfected by multiple parasite strains and species, and interactions between parasites within hosts are known to influence parasite prevalence and diversity, as well as epidemic timing. Importantly, interactions between coinfecting parasites can be affected by the order in which they infect hosts (i.e. within‐host priority effects). In this study, we use a single‐host, two‐pathogen, SI model with environmental transmission to explore how within‐host priority effects scale up to alter host population‐scale infection patterns. Specifically, we ask how parasite prevalence changes in the presence of different types of priority effects. We consider two scenarios without priority effects and four scenarios with priority effects where there is either an advantage or a disadvantage to being the first to infect in a coinfected host. Models without priority effects always predict negative relationships between the prevalences of both parasites. In contrast, models with priority effects can yield unimodal prevalence relationships where the prevalence of a focal parasite is minimized or maximized at intermediate prevalences of a coinfecting parasite. The mechanism behind this pattern is that as the prevalence of the coinfecting parasite increases, most infections of the focal parasite change from occurring as solo infections, to first arrival coinfections, to second arrival coinfections. The corresponding changes in parasite fitness as the focal parasite moves from one infection class to another then map to changes in focal parasite prevalence. Further, we found that even when parasites interact negatively within a host, they still can have positive prevalence relationships at the population scale. These results suggest that within‐host priority effects can change host population‐scale infection patterns in systematic (and initially counterintuitive) ways, and that taking them into account may improve disease forecasting in coinfected populations.     

Can helminth community patterns be amplified when transferred by predation from intermediate to definitive hosts?

Helminth communities in definitive hosts are formed by the acquisition of packets of larvae arriving each time an intermediate host is consumed. It is thus possible that associations between parasite species or other aspects of community structure get transferred from intermediate to definitive hosts. Earlier computer simulations showed that associations between 2 parasite species, in particular positive associations, could be transferred up the food chain. Here, we alter some of the assumptions of previous models and generate new simulations of several ways in which source infracommunities in intermediate hosts can be transferred to target infracommunities in definitive hosts. In particular, we introduced nonrandom selection of intermediate hosts by predatory definitive hosts, to mimic the phenomenon of host manipulation by parasites; this consisted in biasing predation toward intermediate hosts harboring a certain parasite species. Overall, our results show that positive covariances between 2 parasite species can not only be transferred but can also be amplified during transmission to definitive hosts; significant covariance between parasite species can even appear in the definitive hosts when none existed in the intermediate hosts. Negative covariance was not as readily transferred to definitive hosts and amplified, in part because of properties of the presence-absence covariance index. Amplification of covariance results from intermediate host manipulation as well as from other processes taking place during transmission. These results suggest that the patterns of association between helminth species in definitive hosts cannot be taken to reflect the processes acting inside those hosts: they may simply be inherited, with amplification, from intermediate hosts.     

Parasites on an intertidal Corophium-bed: factors determining the phenology of microphallid trematodes in the intermediate host populations of the mud-snail Hydrobia ulvae and the amphipod Corophium volutator

The phenology of microphallid trematodes within their intermediate hostpopulations has been studied on an intertidal mud flat. The parasites usethe mud snail Hydrobia ulvae and the infaunal amphipod Corophium volutatoras first and secondary intermediate host, respectively. Migratory shorebirdsact as final hosts. Our results show a general trend of decline in thedensity of infected intermediate hosts during both spring and autumn, whichcould mainly be ascribed to shorebird predation. During summer the densityof both infected snails and infected amphipods increased considerably, witha culmination in June within the snail population (1000 infectedm-² and in August within the amphipod population (40 000infected m-². This time lag in parasite occurrence could berelated to (1) the development time of larval trematodes within the snails,(2) higher ambient temperatures in late summer increasing parasitetransmission between snails and amphipods during this period, and (3) ageneral increase in the Corophium population during late summer. Fromsamples collected between 1990 and 1995 it is shown that microphallidtrematodes occasionally may give rise to mass mortality in the amphipodpopulation. The prerequisites for such an event are a high parasiteprevalence within the first intermediate host population and unusually highambient temperatures, facilitating parasite transmission to the secondaryintermediate host, C. volutator.     

Spatial covariation between infection levels and intermediate host densities in two trematode species

Both theoretical arguments and empirical evidence suggest that parasite transmission depends on host density. In helminths with complex life cycles, however, it is not clear which host, if any, is the most important. Here, the relationships between the abundance of metacercariae in second intermediate hosts, and the local density of both the first and second intermediate hosts of two trematode species, are investigated. Samples of the snail Potamopyrgus antipodarum, the amphipod Paracalliope fluviatilis and the isopod Austridotea annectens were collected from ten stations in a New Zealand lake. In the trematode Coitocaecum parvum, neither the density of the snail first intermediate host nor that of the amphipod second intermediate host correlated with infection levels in amphipods. In contrast, in the trematode Microphallus, infection levels in isopod second intermediate hosts were positively associated with isopod density and negatively associated with the density of snail first intermediate hosts. These relationships are explained by a negative correlation between snail and isopod densities, mediated in part by their different use of macrophyte beds in the lake. Overall, the results suggest that, at least for Microphallus, local infection levels depend on local intermediate host densities.     

The evolution of complex life cycles when parasite mortality is size- or time-dependent

In complex cycles, helminth larvae in their intermediate hosts typically grow to a fixed size. We define this cessation of growth before transmission to the next host as growth arrest at larval maturity (GALM). Where the larval parasite controls its own growth in the intermediate host, in order that growth eventually arrests, some form of size- or time-dependent increase in its death rate must apply. In contrast, the switch from growth to sexual reproduction in the definitive host can be regulated by constant (time-independent) mortality as in standard life history theory. We here develop a step-wise model for the evolution of complex helminth life cycles through trophic transmission, based on the approach of Parker et al. [2003a. Evolution of complex life cycles in helminth parasites. Nature London 425, 480-484], but which includes size- or time-dependent increase in mortality rate. We assume that the growing larval parasite has two components to its death rate: (i) a constant, size- or time-independent component, and (ii) a component that increases with size or time in the intermediate host. When growth stops at larval maturity, there is a discontinuous change in mortality to a constant (time-independent) rate. This model generates the same optimal size for the parasite larva at GALM in the intermediate host whether the evolutionary approach to the complex life cycle is by adding a new host above the original definitive host (upward incorporation), or below the original definitive host (downward incorporation). We discuss some unexplored problems for cases where complex life cycles evolve through trophic transmission.     

Of mice and worms: are co-infections with unrelated parasite strains more damaging to definitive hosts?

Intraspecific competition between co-infecting parasites can influence the amount of virulence, or damage, they do to their host. Kin selection theory dictates that infections with related parasite individuals should have lower virulence than infections with unrelated individuals, because they benefit from inclusive fitness and increased host longevity. These predictions have been tested in a variety of microparasite systems, and in larval stage macroparasites within intermediate hosts, but the influence of adult macroparasite relatedness on virulence has not been investigated in definitive hosts. This study used the human parasite Schistosoma mansoni to determine whether definitive hosts infected with related parasites experience lower virulence than hosts infected with unrelated parasites, and to compare the results from intermediate host studies in this system. The presence of unrelated parasites in an infection decreased parasite infectivity, the ability of a parasite to infect a definitive host, and total worm establishment in hosts, impacting the less virulent parasite strain more severely. Unrelated parasite co-infections had similar virulence to the more virulent of the two parasite strains. We combine these findings with complementary studies of the intermediate snail host and describe trade-offs in virulence and selection within the life cycle. Damage to the host by the dominant strain was muted by the presence of a competitor in the intermediate host, but was largely unaffected in the definitive host. Our results in this host–parasite system suggest that unrelated infections may select for higher virulence in definitive hosts while selecting for lower virulence in intermediate hosts.     

Parasite-induced trophic facilitation exploited by a non-host predator: a manipulator's nightmare

Parasites with complex life cycles, relying on trophic transmission to a definitive host, very often induce changes in the behaviour or appearance of their intermediate hosts. Because this usually makes the intermediate host vulnerable to predation by the definitive host, it is generally assumed that the parasite's transmission rate is increased, and that the modification of the host is, therefore, of great adaptive significance to the parasite. However, in the ecological "real world" other predators unsuitable as hosts may just as well take advantage of the facilitation process and significantly erode the benefit of host manipulation. Here we show that the intertidal New Zealand cockle (Austrovenus stutchburyi), manipulated by its echinostome trematode (Curtuteria australis) to rest on the sediment surface fully exposed to predation from the avian definitive host, is also subject to sublethal predation from a benthic feeding fish (Notolabrus celidotus, Labridae). The fish is targeting only the cockle-foot, in which the parasite preferentially encysts, reducing the infection intensity of manipulated cockles to levels comparable with those in non-manipulated, buried cockles. Based on the frequency and intensity of the foot cropping and predation rates on surfaced cockles by avian hosts, it is estimated that 2.5% of the parasite population in manipulated cockles is transmitted successfully whereas 17.1% is lost to fish. We argue that the adaptive significance of manipulation in the present system depends critically on the feeding behaviour of the definitive host. If cockles constitute the majority of prey items, there will be selection against manipulation. If manipulated cockles are taken as an easily accessible supplement to a diet composed mostly of other prey organisms, behavioural manipulation of the cockle host appears a high risk, high profit transmission strategy. Both these feeding behaviours of birds are known to occur in the field.