Parasite transmission modes and the evolution of virulence

A mathematical model is presented that explores the relationship between transmission patterns and the evolution of virulence for horizontally transmitted parasites when only a single parasite strain can infect each host. The model is constructed by decomposing parasite transmission into two processes, the rate of contact between hosts and the probability of transmission per contact. These transmission rate components, as well as the total parasite mortality rate, are allowed to vary over the course of an infection. A general evolutionarily stable condition is presented that partitions the effects of virulence on parasite fitness into three components: fecundity benefits, mortality costs, and morbidity costs. This extension of previous theory allows us to explore the evolutionary consequences of a variety of transmission patterns. I then focus attention on a special case in which the parasite density remains approximately constant during an infection, and I demonstrate two important ways in which transmission modes can affect virulence evolution: by imposing different morbidity costs on the parasite and by altering the scheduling of parasite reproduction during an infection. Both are illustrated with examples, including one that examines the hypothesis that vector-borne parasites should be more virulent than non-vector-borne parasites (Ewald 1994). The validity of this hypothesis depends upon the way in which these two effects interact, and it need not hold in general.     

Evolution of virulence under intensive farming: salmon lice increase skin lesions and reduce host growth in salmon farms

Parasites rely on resources from a host and are selected to achieve an optimal combination of transmission and virulence. Human‐induced changes in parasite ecology, such as intensive farming of hosts, might not only favour increased parasite abundances, but also alter the selection acting on parasites and lead to life‐history evolution. The trade‐off between transmission and virulence could be affected by intensive farming practices such as high host density and the use of antiparasitic drugs, which might lead to increased virulence in some host–parasite systems. To test this, we therefore infected Atlantic salmon (Salmo salar) smolts with salmon lice (Lepeophtheirus salmonis) sampled either from wild or farmed hosts in a laboratory experiment. We compared growth and skin damage (i.e. proxies for virulence) of hosts infected with either wild or farmed lice and found that, compared to lice sampled from wild hosts in unfarmed areas, those originating from farmed fish were more harmful; they inflicted more skin damage to their hosts and reduced relative host weight gain to a greater extent. We advocate that more evolutionary studies should be carried out using farmed animals as study species, given the current increase in intensive food production practices that might be compared to a global experiment in parasite evolution.     

Mosquito mortality and the evolution of malaria virulence

Abstract Several laboratory studies of malaria parasites (Plasmodium sp.) and some field observations suggest that parasite virulence, defined as the harm a parasite causes to its vertebrate host, is positively correlated with transmission. Given this advantage, what limits the continual evolution of higher parasite virulence? One possibility is that while more virulent strains are more infectious, they are also more lethal to mosquitoes. In this study, we tested whether the virulence of the rodent malaria parasite P. chabaudi in the laboratory mouse was correlated with the fitness of mosquitoes it subsequently infected. Mice were infected with one of seven genetically distinct clones of P. chabaudi that differ in virulence. Weight loss and anemia in infected mice were monitored for 16–17 days before Anopheles stephensi mosquitoes were allowed to take a blood meal from them. Infection virulence in mice was positively correlated with transmission to mosquitoes (infection rate) and weakly associated with parasite burden (number of oocysts). Mosquito survival fell with increasing oocyst burden, but there was no overall statistically significant relationship between virulence in mice and mosquito mortality. Thus, there was no evidence that more virulent strains are more lethal to mosquitoes. Both vector survival and fecundity depended on parasite clone, and contrary to expectations, mosquitoes fed on infections more virulent to mice were more fecund. The strong parasite genetic effects associated with both fecundity and survival suggests that vector fitness could be an important selective agent shaping malaria population genetics and the evolution of phenotypes such as virulence in the vector.     

Effectively vertical transmission of a Drosophila‐parasitic nematode: mechanism and consequences

1. Long‐term control of insects by parasites is possible only if the parasite populations persist. Because parasite transmission rate depends on host density, parasite populations may go extinct during periods of low host density. Vertical transmission of parasites, however, is independent of host density and may therefore provide a demographic bridge through times when their insect hosts are rare. 2. The nematode Howardula aoronymphium, which parasitises mycophagous species of Drosophila, can experience both horizontal and effectively vertical transmission, relative rates of which depend, in theory at least, on the density of hosts at breeding sites. 3. A nine‐generation experiment was carried out in which nematodes were transmitted either exclusively vertically or primarily horizontally. This experiment revealed that these parasites can persist and exhibit positive population growth even when there is only vertical transmission. 4. Assays at the end of the experiment revealed that the vertically transmitted nematodes had suffered no inbreeding depression and that they were similar to the horizontally transmitted nematodes in terms of virulence, infectivity, within‐host growth rate, and fecundity. Thus, vertical transmission of H. aoronymphium did not appear to compromise the ability of these parasites to control Drosophila populations.     

The virulence–transmission relationship in an obligate killer holds under diverse epidemiological and ecological conditions,but where is the tradeoff?

Parasite virulence is a leading theme in evolutionary biology. Modeling the course of virulence evolution holds the promise of providing practical insights into the management of infectious diseases and the implementation of vaccination strategies. A key element of virulence modeling is a tradeoff between parasite transmission rate and host lifespan. This assumption is crucial for predicting the level of optimal virulence. Here, I test this assumption using the water flea Daphnia magna and its castrating and obligate‐killing bacterium Pasteuria ramosa. I found that the virulence–transmission relationship holds under diverse epidemiological and ecological conditions. In particular, parasite genotype, absolute and relative parasite dose, and within‐host competition in multiple infections did not significantly affect the observed trend. Interestingly, the relationship between virulence and parasite transmission in this system is best explained by a model that includes a cubic term. Under this relationship, parasite transmission initially peaks and saturates at an intermediate level of virulence, but then it further increases as virulence decreases, surpassing the previous peak. My findings also highlight the problem of using parasite‐induced host mortality as a “one‐size‐fits‐all” measure of virulence for horizontally transmitted parasites, without considering the onset and duration of parasite transmission as well as other equally virulent effects of parasites (e.g., host castration). Therefore, mathematical models may be required to predict whether these particular characteristics of horizontally transmitted parasites can direct virulence evolution into directions not envisaged by existing models.     

Strength in numbers: high parasite burdens increase transmission of a protozoan parasite of monarch butterflies (<Emphasis Type="Italic">Danaus plexippus</Emphasis>)

Parasites often produce large numbers of offspring within their hosts. High parasite burdens are thought to be important for parasite transmission, but can also lower host fitness. We studied the protozoan Ophryocystis elektroscirrha, a common parasite of monarch butterflies (Danaus plexippus), to quantify the benefits of high parasite burdens for parasite transmission. This parasite is transmitted vertically when females scatter spores onto eggs and host plant leaves during oviposition; spores can also be transmitted between mating adults. Monarch larvae were experimentally infected and emerging adult females were mated and monitored in individual outdoor field cages. We provided females with fresh host plant material daily and quantified their lifespan and lifetime fecundity. Parasite transmission was measured by counting the numbers of parasite spores transferred to eggs and host plant leaves. We also quantified spores transferred from infected females to their mating partners. Infected monarchs had shorter lifespans and lower lifetime fecundity than uninfected monarchs. Among infected females, those with higher parasite loads transmitted more parasite spores to their eggs and to host plant leaves. There was also a trend for females with greater parasite loads to transmit more spores to their mating partners. These results demonstrate that high parasite loads on infected butterflies confer a strong fitness advantage to the parasite by increasing between-host transmission.     

Virulence and age at reproduction: new insights into host–parasite coevolution

We consider an explicit mutation–selection process to investigate the dynamics underlying the coevolution of parasite’s virulence and host’s prereproductive life span in a system with discrete generations. Conforming with earlier models, our model predicts that virulence generally increases with natural mortality of the host, and that a moderate increase in virulence selects for lower ages at reproduction. However, the epidemiological feedback in our model also gives rise to unusual and unexpected patterns. In particular, if virulence is sufficiently high the model can lead to a bifurcation pattern, where two strategies coexist in the host population. The first is to develop rapidly to reproduce before being infected. Individuals following this strategy suffer, however, from reduced fecundity. The second strategy is to develop much more slowly. Because of the high virulence, the effective period of transmission is short, so that a few slowly developing individuals escape infection. These individuals, although choosing a risky strategy, benefit from high fecundity.     

The expression of virulence during double infections by different parasites with conflicting host exploitation and transmission strategies

In many natural populations, hosts are found to be infected by more than one parasite species. When these parasites have different host exploitation strategies and transmission modes, a conflict among them may arise. Such a conflict may reduce the success of both parasites, but could work to the benefit of the host. For example, the less‐virulent parasite may protect the host against the more‐virulent competitor. We examine this conflict using the waterflea Daphnia magna and two of its sympatric parasites: the blood‐infecting bacterium Pasteuria ramosa that transmits horizontally and the intracellular microsporidium Octosporea bayeri that can concurrently transmit horizontally and vertically after infecting ovaries and fat tissues of the host. We quantified host and parasite fitness after exposing Daphnia to one or both parasites, both simultaneously and sequentially. Under conditions of strict horizontal transmission, Pasteuria competitively excluded Octosporea in both simultaneous and sequential double infections, regardless of the order of exposure. Host lifespan, host reproduction and parasite spore production in double infections resembled those of single infection by Pasteuria. When hosts became first vertically (transovarilly) infected with O. bayeri, Octosporea was able to withstand competition with P. ramosa to some degree, but both parasites produced less transmission stages than they did in single infections. At the same time, the host suffered from reduced fecundity and longevity. Our study demonstrates that even when competing parasite species utilize different host tissues to proliferate, double infections lead to the expression of higher virulence and ultimately may select for higher virulence. Furthermore, we found no evidence that the less‐virulent and vertically transmitting O. bayeri protects its host against the highly virulent P. ramosa.     

The evolution of host protection by vertically transmitted parasites

Hosts are often infected by a variety of different parasites, leading to competition for hosts and coevolution between parasite species. There is increasing evidence that some vertically transmitted parasitic symbionts may protect their hosts from further infection and that this protection may be an important reason for their persistence in nature. Here, we examine theoretically when protection is likely to evolve and its selective effects on other parasites. Our key result is that protection is most likely to evolve in response to horizontally transmitted parasites that cause a significant reduction in host fecundity. The preponderance of sterilizing horizontally transmitted parasites found in arthropods may therefore explain the evolution of protection seen by their symbionts. We also find that protection is more likely to evolve in response to highly transmissible parasites that cause intermediate, rather than high, virulence (increased death rate when infected). Furthermore, intermediate levels of protection select for faster, more virulent horizontally transmitted parasites, suggesting that protective symbionts may lead to the evolution of more virulent parasites in nature. When we allow for coevolution between the symbiont and the parasite, more protection is likely to evolve in the vertically transmitted symbionts of longer lived hosts. Therefore, if protection is found to be common in nature, it has the potential to be a major selective force on host–parasite interactions.     

PARASITE CO‐TRANSMISSION AND THE EVOLUTIONARY EPIDEMIOLOGY OF VIRULENCE

Hosts are often co‐infected by several parasite genotypes of the same species or even by different species and this is known to affect virulence evolution. However, epidemiological models typically assume that only one of the co‐infecting strains can be transmitted at the same time, which is often at odds with the observed biology. Here, I study the effect of co‐transmission on virulence evolution in a case where parasites compete for host resources. For co‐infections by strains of the same species, increased co‐transmission selects for less virulent strains. This is because co‐transmission aligns the interests of co‐infecting strains, thus decreasing the selective pressure for increased within‐host competitiveness. For co‐infection caused by different parasite species, the evolutionary outcome depends on the respective virulence of the two parasite species. Finally, I investigate asymmetric scenarios, for example that of plant viruses that require “helper” molecules produced by viruses from another species to be transmitted. These results show that even if parasite strains compete for host resources, the prevalence of co‐infections can be a poor predictor of virulence evolution.     

Reduced growth in wild juvenile sockeye salmon Oncorhynchus nerka infected with sea lice

Daily growth rings were examined in the otoliths of wild juvenile sockeye salmon Oncorhynchus nerka to determine whether infection by ectoparasitic sea lice Caligus clemensi and Lepeophtheirus salmonis was associated with reduced host body growth, an important determinant of survival. Over 98% of the sea lice proved to be C. clemensi and the fish that were highly infected grew more slowly than uninfected individuals. Larger fish also grew faster than smaller fish. Finally, there was evidence of an interaction between body size and infection status, indicating the potential for parasite‐mediated growth divergence.     

THE INFLUENCE OF HOST DEMOGRAPHY ON THE EVOLUTION OF VIRULENCE OF A MICROSPORIDIAN GUT PARASITE

It is predicted that host exploitation should evolve to maximize parasite fitness and that virulence (= parasite-induced host mortality) evolves along with the rate of host exploitation. If the life expectancy of a parasite is short, it is expected to evolve a higher rate of host exploitation and therefore higher virulence because the penalty to the parasite for killing the host is reduced. We tested this hypothesis by keeping for 14 months the horizontally transmitted microsporidian parasite Glugoides intestinalis in mono-clonal host cultures (Daphnia magna) under conditions of high and low host background mortality. High host mortality, and thus parasite mortality, was achieved by replacing weekly 70–80% of all hosts in a culture with uninfected hosts from stock cultures (Replacement lines). In the low-mortality treatment no replacement took place. Contrary to our expectation, parasites from the Replacement lines evolved a lower within-host growth rate and virulence than parasites from the Nonreplacement lines. Across lines we found a strong positive correlation between within-host growth rate and virulence. We did further experiments to answer the question why our data did not support the predictions. Sporophorous vesicles (SVs, spore clusters) were smaller in doubly infected than in singly infected host-gut cells, indicating that competition within cells bears costs for the parasite. Due to our experimental protocol, the average life span of infections had been much higher in the Nonreplacement lines. Since the number of parasites inside a host increases with the time since infection, long-lasting infections led to high frequencies of multiply infected host-gut cells. Therefore, we speculated that within-cell competition was more severe in the Nonreplacement lines and may have led to selection for accelerated within-host growth. SVs in the Nonreplacement lines were indeed significantly larger. Our results point out that single-factor explanations for the evolution of virulence can lead to wrong predictions and that multiple infections are an important factor in virulence evolution.     

The evolution of reduced antagonism—A role for host–parasite coevolution

Why do some host–parasite interactions become less antagonistic over evolutionary time? Vertical transmission can select for reduced antagonism. Vertical transmission also promotes coevolution between hosts and parasites. Therefore, we hypothesized that coevolution itself may underlie transitions to reduced antagonism. To test the coevolution hypothesis, we selected for reduced antagonism between the host Caenorhabditis elegans and its parasite Serratia marcescens. This parasite is horizontally transmitted, which allowed us to study coevolution independently of vertical transmission. After 20 generations, we observed a response to selection when coevolution was possible: reduced antagonism evolved in the copassaged treatment. Reduced antagonism, however, did not evolve when hosts or parasites were independently selected without coevolution. In addition, we found strong local adaptation for reduced antagonism between replicate host/parasite lines in the copassaged treatment. Taken together, these results strongly suggest that coevolution was critical to the rapid evolution of reduced antagonism.     

Virulence and transmission modes in metapopulations: when group selection increases virulence

Individuals that are infected by a pathogen can transmit it to unrelated conspecifics (horizontal transmission) or to their progeny when they reproduce (vertical transmission). The mechanisms of these two routes of transmission are different and this difference impacts the way virulence evolves in pathogens. More precisely, horizontal transmission depends on the probability that an infected host contacts susceptible conspecifics, and therefore on its lifespan. Vertical transmission additionally depends on the host's fecundity. This additional dependence in vertically transmitted pathogens results in a decrease in their evolutionarily stable (ES) virulence.Spatial structure is another factor that is often supposed to decrease pathogens’ ES virulence, mostly because it impedes competition for transmission in local populations of hosts. In this paper, using the adaptive dynamics framework, we show that spatial structure can increase ES virulence when pathogens are mostly vertically transmitted. This is due to the difference in how pathogens compete for transmission in local population of hosts, depending on how they are transmitted. We also show that symbionts that are horizontally transmitted should respond more to a change in spatial structure than symbionts that are vertically transmitted.     

Sea lice and salmon population dynamics: effects of exposure time for migratory fish

The ecological impact of parasite transmission from fish farms is probably mediated by the migration of wild fishes, which determines the period of exposure to parasites. For Pacific salmon and the parasitic sea louse, Lepeophtheirus salmonis, analysis of the exposure period may resolve conflicting observations of epizootic mortality in field studies and parasite rejection in experiments. This is because exposure periods can differ by 2–3 orders of magnitude, ranging from months in the field to hours in experiments. We developed a mathematical model of salmon–louse population dynamics, parametrized by a study that monitored naturally infected juvenile salmon held in ocean enclosures. Analysis of replicated trials indicates that lice suffer high mortality, particularly during pre-adult stages. The model suggests louse populations rapidly decline following brief exposure of juvenile salmon, similar to laboratory study designs and data. However, when the exposure period lasts for several weeks, as occurs when juvenile salmon migrate past salmon farms, the model predicts that lice accumulate to abundances that can elevate salmon mortality and depress salmon populations. The duration of parasite exposure is probably critical to salmon–louse population dynamics, and should therefore be accommodated in coastal planning and management where fish farms are situated on wild fish migration routes.     

Conflict between parasites with different transmission strategies infecting an amphipod host

Competition between parasites within a host can influence the evolution of parasite virulence and host resistance, but few studies examine the effects of unrelated parasites with conflicting transmission strategies infecting the same host. Vertically transmitted (VT) parasites, transmitted from mother to offspring, are in conflict with virulent, horizontally transmitted (HT) parasites, because healthy hosts are necessary to maximize VT parasite fitness. Resolution of the conflict between these parasites should lead to the evolution of one of two strategies: avoidance, or sabotage of HT parasite virulence by the VT parasite. We investigated two co-infecting parasites in the amphipod host, Gammarus roeseli: VT microsporidia have little effect on host fitness, but acanthocephala modify host behaviour, increasing the probability that the amphipod is predated by the acanthocephalan's definitive host. We found evidence for sabotage: the behavioural manipulation induced by the Acanthocephala Polymorphus minutus was weaker in hosts also infected by the microsporidia Dictyocoela sp. (roeselum) compared to hosts infected by P. minutus alone. Such conflicts may explain a significant portion of the variation generally observed in behavioural measures, and since VT parasites are ubiquitous in invertebrates, often passing undetected, conflict via transmission may be of great importance in the study of host-parasite relationships.     

THE EVOLUTIONARY IMPLICATIONS OF CONFLICT BETWEEN PARASITES WITH DIFFERENT TRANSMISSION MODES

Understanding the processes that shape the evolution of parasites is a key challenge for evolutionary biology. It is well understood that different parasites may often infect the same host and that this may have important implications to the evolutionary behavior. Here we examine the evolutionary implications of the conflict that arises when two parasite species, one vertically transmitted and the other horizontally transmitted, infect the same host. We show that the presence of a vertically transmitted parasite (VTP) often leads to the evolution of higher virulence in horizontally transmitted parasites (HTPs), particularly if the VTPs are feminizing. The high virulence in some HTPs may therefore result from coinfection with cryptic VTPs. The impact of an HTP on a VTP evolution depends crucially on the nature of the life‐history trade‐offs. Fast virulent HTPs select for intermediate feminization and virulence in VTPs. Coevolutionary models show similar insights, but emphasize the importance of host life span to the outcome, with higher virulence in both types of parasite in short‐lived hosts. Overall, our models emphasize the interplay of host and parasite characteristics in the evolutionary outcome and point the way for further empirical study.     

PARASITE VIRULENCE AND HOST IMMUNE DEFENSE: HOST IMMUNE RESPONSE IS RELATED TO NEST REUSE IN BIRDS

The evolution of parasite virulence has been hypothesized to be related to the mode of parasite transmission; horizontally transmitted parasites can afford to damage their hosts more than vertically transmitted parasites because increased virulence does not reduce the probability of transmission to new hosts. This relationship between mode of transmission and virulence would particularly select for improved immune defense in hosts that are subject to horizontally transmitted parasites. Among avian hosts, hole nesters and colonial nesters frequently reuse nest sites because of nest-site limitation, and this results in an increased frequency of horizontal transmission. Comparison of the size of two organs involved in the immune defense between pairs of bird species being either hole or open nesters, or colonially or solitarily nesting birds, respectively, revealed that the size of the bursa of Fabricius and the spleen were consistently larger in hole nesters than in open nesters, and similarly in colonially breeding bird species than in solitarily breeding species. These results support the hypothesis that mode of parasite transmission affects the evolution of immune defence in hosts.     

Local adaptation and enhanced virulence of Nosema granulosis artificially introduced into novel populations of its crustacean host, Gammarus duebeni

Local adaptation theory predicts that, on average, most parasite species should be locally adapted to their hosts (more suited to hosts from local than distant populations). Local adaptation has been studied for many horizontally transmitted parasites, however, vertically transmitted parasites have received little attention. Here we present the first study of local adaptation in an animal/parasite system where the parasite is vertically transmitted. We investigate local adaptation and patterns of virulence in a crustacean host infected with the vertically transmitted microsporidian Nosema granulosis. Nosema granulosis is vertically transmitted to successive generations of its crustacean host, Gammarus duebeni and infects up to 46% of adult females in natural populations. We investigate local adaptation using artificial horizontal infection of different host populations in the UK. Parasites were artificially inoculated from a donor population into recipient hosts from the sympatric population and into hosts from three allopatric populations in the UK. The parasite was successfully established in hosts from all populations regardless of location, infecting 45% of the recipients. Nosema granulosis was vertically (transovarially) transmitted to 39% of the offspring of artificially infected females. Parasite burden (intensity of infection) in developing embryos differed significantly between host populations and was an order of magnitude higher in the sympatric population, suggesting some degree of host population specificity with the parasite adapted to its local host population. In contrast with natural infections, artificial infection with the parasite resulted in substantial virulence, with reduced host fecundity (24%) and survival (44%) of infected hosts from all the populations regardless of location. We discuss our findings in relation to theories of local adaptation and parasite-host coevolution.     

Vertically transmitted symbiont reduces host fitness along temperature gradient

Parasites with exclusive vertical transmission from host parent to offspring are an evolutionary puzzle. With parasite fitness entirely linked to host reproduction, any fitness cost for infected hosts risks their selective elimination. Environmental conditions likely influence parasite impact and thereby the success of purely vertical transmission strategies. We tested for temperature‐dependent virulence of Caedibacter taeniospiralis, a vertically transmitted bacterial symbiont of the protozoan Paramecium tetraurelia. We compared growth of infected and cured host populations at five temperatures (16–32 °C). Infection reduced host density at all temperatures, with a peak of ?30% at 28 °C. These patterns were largely consistent across five infected Paramecium strains. Similar to Wolbachia symbionts, C. taeniospiralis may compensate fitness costs by conferring to the host a ‘killer trait’, targeting uninfected competitors. Considerable loss of infection at 32 °C suggests that killer efficacy is not universal and that limited heat tolerance restricts the conditions for persistence of C. taeniospiralis.