Parasites And Their Virulence Essay, Research Paper

ABSTRACT

Why do some parasites kill the host they depend upon while

others coexist with their host? Two prime factors determine parasitic

virulence: the manner in which the parasite is transmitted, and the

evolutionary history of the parasite and its host. Parasites which

have colonized a new host species tend to be more virulent than

parasites which have coevolved with their hosts. Parasites which are

transmitted horizontally tend to be more virulent than those

transmitted vertically. It has been assumed that parasite-host

interactions inevitably evolve toward lower virulence. This is

contradicted by studies in which virulence is conserved or increases

over time. A model which encompasses the variability of parasite-host

interactions by synthesizing spatial (transmission) and temporal

(evolutionary) factors is examined. Lenski and May (1994) and Antia et

al. (1993) predict the modulation of virulence in parasite-host

systems by integrating evolutionary and transmissibility factors.

INTRODUCTION

Why do certain parasites exhibit high levels of virulence within

their host populations while others exhibit low virulence? The two

prime factors most frequently cited (Esch and Fernandez 1993, Toft et

al. 1991) are evolutionary history and mode of transmission.

Incongruently evolved parasite-host associations are characterized by

high virulence, while congruent evolution may result in reduced

virulence (Toft et al. 1991). Parasites transmitted vertically (from

parent to offspring) tend to be less virulent than parasites

transmitted horizontally (between unrelated individuals of the same or

different species). Studies in which virulence is shown to increase

during parasite-host interaction, as in Ebert’s (1994) experiment with

Daphnia magna, necessitate a synthesis of traditionally discrete

factors to predict a coevolutionary outcome. Authors prone to

habitually use the word decrease before the word virulence are

encouraged to replace the former with modulate, which emphasizes the

need for an inclusive, predictive paradigm for parasite-host

interaction.

Evolutionary history and mode of transmission will first be

considered separately, then integrated using an equation discussed

by Antia et al. (1993) and a model proposed by Lenski and May (1994).

Transmission is a spatial factor, defined by host density and specific

qualities of host-parasite interaction, which gives direction to the

modulation of virulence. Evolution is a temporal factor which

determines the extent of the modulation. The selective pressures of

the transmission mode act on parasite populations over evolutionary

time, favoring an equilibrium level of virulence (Lenski and May

1994).

DOES COEVOLUTION DETERMINE VIRULENCE?

Incongruent evolution is the colonization of a new host species

by a parasite. It is widely reported that such colonizations, when

successful, feature high virulence due to the lack of both evolved

host defenses and parasitic self-regulation (Esch and Fernandez 1993,

Toft et al. 1991). Unsuccessful colonizations must frequently occur

when parasites encounter hosts with adequate defenses. In Africa,

indigenous ruminants experience low virulence from Trypanosoma brucei

infection, while introduced ruminants suffer fatal infections (Esch

and Fernandez 1993). There has been no time for the new host to

develop immunity, or for the parasite to self-regulate. Virulent

colonizations may occur regularly in epizootic-enzootic cycles. Sin

Nombre virus, a hemmorhagic fever virus, was epizootic in 1993 after

the population of its primary enzootic host, Peromyscus maniculatus,

had exploded, increasing the likelihood of transmission to humans

(Childs et al. 1995). Sin Nombre exhibited unusually high mortality in

human populations (Childs et al. 1995), which were being colonized by

the parasite.

It is assumed that coevolution of parasite and host will result

in decreased virulence (Esch and Fernandez 1993, Toft et al. 1991).

Sin Nombre virus was found to infect 30.4 % of the P. maniculatus

population, exhibiting little or no virulence in the mice (Childs et

al. 1995). Similar low levels of virulence have been found in the

enzootic rodent hosts of Yersinia pestis (Gage et al. 1995). In

Australia, decreased grades of virulence of myxoma virus have been

observed in rabbit populations since the virus was introduced in 1951

(Krebs C. J. 1994). Many of the most widespread parasites exhibit low

virulence, suggesting that success in parasite suprapopulation range

and abundance may be the result of reduction in virulence over time.

Hookworms are present in the small intestines of one-fifth of the

world’s human population and rarely induce mortality directly

(Hotez 1995).

Evolution toward a higher level of virulence has been regarded

as an unexplainable anomaly. Parasites which do less harm presumably

have an advantage throughout a long coevolutionary association with

their hosts. Ebert’s (1994) experiment with the planktonic crustacean

Daphnia magna and its horizontally transmitted parasite Pleistophora

intestinalis suggests that coevolution does not determine the

direction of the modulation of virulence. Virulence decreased with the

geographic distance between sites of origin where the host and

parasite were collected (Ebert 1994). Thus, the parasite was

significantly more virulent in hosts it coexisted with in the wild

than it was in novel hosts. Many viruses, such as Rabies (Lyssavirus

spp.), persist in natural populations while maintaining high levels of

virulence in all potential hosts (Krebs, J. W. 1995). Extinction is

not an inevitable outcome of increased virulence (Lenski and May

1994). Increased or conserved virulence during coevolution calls

into question long held assumptions about the effect of coevolution on

parasitic virulence (Gibbons 1994). Parasitic virulence frequently

changes over coevolutionary time, but the length of parasite-host

association does not account for the virulence of the parasite.

Transmission has been identified as the factor which determines the

level of parasitic virulence (Read and Harvey 1993).

TRANSMISSION AND THE DIRECTION OF MODULATION

Herre’s (1993) experiment with fig wasps (Pegoscapus spp.) and

nematodes (Parasitodiplogaster spp.) illustrates the effect of

transmission mode on parasitic virulence. When a single female wasp

inhabited a fig, all transmission of the parasite was vertical, from

the female to her offspring. The parasite’s fitness was intimately

tied to the fecundity of the host upon which it had arrived. When a

fig was inhabited by several foundress wasps, horizontal transmission

between wasp families was possible. In the figs inhabited by a single

foundress wasp, Herre found that less virulent species of the nematode

were successful, while in figs containing multiple foundress wasps,

more virulent species of the nematode were successful. Greater

opportunity to find alternate hosts resulted in less penalty for

lowering host fecundity. More virulent nematodes had an adaptive

advantage when host density was high and horizontal transmission was

possible. When host density was low, nematodes which had less effect

on host fecundity ensured that offspring (i.e. future hosts) would be

available.

Low virulence is characteristic of many vertical transmission

cycles. Certain parasites avoid impairing their host’s fecundity by

becoming dormant within maternal tissue. Toxocara canis larvae reside

in muscles and other somatic tissues of bitches until the 42nd to 56th

day of a 70-day gestation, when they migrate through the placenta,

entering fetal lungs where they remain until birth (Cheney and Hibler

1990). A high proportion of puppies are born with roundworm infection,

which can also be transmitted from bitch to puppy by milk (Cheney and

Hibler 1990). If host density is low, a highly evolved vertical

transmission cycle (which exhibits low virulence in the parent)

ensures the survival of the parasite population.

High virulence is characteristic of horizontal transmission

cycles. In Herre’s (1993) experiment, more virulent parasites were

favored when host density was high and reduction of host fitness was

permissible. Certain parasites benefit from reduced host fitness,

particularly parasites borne by insect vectors (Esch and Fernandez

1993) and parasites whose intermediate host must be ingested by

another organism to complete the parasitic life cycle. By immobilizing

their host, heartworm (Dirofilaria immitis) and malaria (Plasmodium

spp.) increase the likelihood that mosquitoes will successfully ingest

microfilaria or gametocytes along with a blood meal. Heartworm

infestation causes pulmonary hypertension in dogs (Wise 1990),

resulting in lethargy and eventual collapse (Georgi and Georgi 1990).

Host immobility increases the opportunities for female mosquitoes to

find and feed upon hosts (Read and Harvey 1993). Infected dogs have

large numbers of D. immitis microfilaria in their circulatory systems,

again increasing the likelihood of ingestion by the insect. Many

infected dogs eventually die from heartworm, but in the process the

parasite has ensured transmission. Similar debilitating effects have

been observed in tapeworm-stickleback interaction; infected

sticklebacks must swim nearer the water’s surface due to an increased

rate of oxygen consumption caused by the parasite (Keymer and Read

1991). Parasitized sticklebacks are more likely to be seen and eaten

by birds, the next host in the life cycle.

Many horizontally transmitted parasites manipulate specific

aspects of host behavior to facilitate transmission between species.

Host fitness is severely impaired in such interactions. The digenean

D. spathaceum invades the eyes of sticklebacks, increasing the

likelihood of successful predation by birds (Milinski 1990). D.

dendriticum migrate to the brains of infected ants, causing them to

uncontrollably clamp their jaws onto blades of grass, ensuring

ingestion by sheep (Esch and Fernandez 1993, Combes 1991). Infection

of a mammalian brain by rabies (Lyssavirus spp.) alters the host’s

behavior, increasing the chance of conflict with other potential

hosts, while accumulation of rabies virus in the salivary glands

ensures that it is spread by bites (Krebs, J. W. et al. 1995).

Horizontally transmitted parasites which target nervous tissue

increase transmissibility by modifying the host into a suicidal

instrument of transmission.

Transmission factors determining parasitic virulence are the

spatial element in a spatial-temporal dynamic. Host density directly

determines the virulence of parasites which depend upon a single host

species (Herre 1993). Virulence may be increased when transmission

necessitates insect vectors or consumption of the primary host by

another species. Virulence varies inversely with the distance between

potential hosts; this distance is magnified when it is measured

between different species.

THE EQUILIBRIUM MODEL

It has been proposed that there is a coevolutionary arms race

between parasite and host, as the former seeks to circumvent the

defensive adaptations of the latter (Esch and Fernandez 1993). In this

view, parasitic virulence is the result of a dynamic stalemate between

host and parasite. This exemplifies the red queen hypothesis, which

predicts continued stalemate until the eventual extinction of both

species. Benton (1990) notes that the red queen hypothesis ignores the

potential for compromise in such a system. Snails (Biomphalaria

glabrata) resistant to Schistosoma mansoni are at a selective

disadvantage due to the costs associated with resistance (Esch and

Fernandez 1993). A high level of virulence persists in the system

because the snail cannot afford to mount an adequate defense. The arms

race hypothesis assumes that the host population can successfully

counter increasing parasitic virulence with resistance over an

extended period of time. Although an arms race may be sustainable in

some fraction of parasite-host interactions, many hosts (such as B.

Glabrata) cannot participate indeterminately.

An alternative explanation for the reduced virulence of

congruently evolved hosts and parasites is the prudent parasite

hypothesis (Esch and Fernandez 1993), in which parasitic virulence

decreases in response to host mortality. Parasites which are too

virulent drive their hosts, and themselves, to extinction. Parasites

which are less virulent persist in the host population. The prudent

parasite hypothesis helps to account for the variation in

coevolutionary outcome by linking host population dynamics with

virulence, but it fails to describe the individual selective forces

which modulate virulence over time. The prudent parasite hypothesis

serves as the theoretical framework in which the factors determining

parasitic virulence can be synthesized. Antia et al. (1993) and Lenski

and May (1994) propose a tradeoff between transmissibility and induced

host mortality which predicts that parasites will evolve toward a

level of virulence which strikes an equilibrium in the parasite-host

system. Equilibrium models suggest that P. intestinalis, which evolved

a higher (yet appropriate) level of virulence in its host (Ebert

1994), is a prudent parasite. Antia et al. (1993) use an equation

developed by May and Anderson in 1983 to examine the tradeoffs in

parasite-host interaction: Ro = (BN) / (a + b + v). Ro is the net

reproductive rate of a parasite, B is the rate parameter for

transmission, N is host density, a is the rate of parasite induced

host mortality, b is the rate of parasite-independent host mortality

and v is the rate of recovery of infected hosts. Parasite populations

grow when transmission or host density increase, when host mortality

decreases or when hosts recover slowly. Studies have established a

positive correlation between transmissibility (B) and host mortality

(a) (Ebert 1994, Antia et al. 1993, Lenski and May 1994). Parasite

populations which exhibit high transmissibility (i.e. virulence)

within a host population are simultaneously lowering host density.

When host density is low, parasites which exhibit high virulence may

kill their hosts before contact with new hosts occurs. Thus,

transmissibility is a spatial factor which describes the likelihood of

contact between hosts and, ultimately, between a parasite and its

host.

Lenski and May (1994) propose an evolutionary sequence in which

parasite populations adapt to the changes they cause in host density

(Fig. 1). A parasite suprapopulation is likely to include a range of

genotypes which are expressed in different potential levels of

virulence (Lenski and May 1994). When host density is high, more

virulent parasites are successful and host density is reduced. At a

lower density of hosts, less virulent strains of the parasite are at a

selective advantage as they increase host survival during infection

and allow more time for transmission to occur. Also, more virulent

strains of the parasite are prone to induce mortality in entire

subsets of the host population, driving themselves to extinction along

with their hosts. This pattern repeats over time, lowering virulence

with each adjustment to declining host population size. Extinction of

the host population is avoided when sufficient variation is present in

the parasite population (Lenski and May 1994).

The evolutionary sequence may be reversed to explain evolution

toward higher virulence when parasitic virulence is below the

equilibrium level. More virulent strains of the parasite outcompete

less virulent strains when host density is above equilibrium.

Conservation of virulence over time occurs when a stable equilibrium

is maintained. Conserved virulence may be high (Lenski and May 1994),

but it reflects stability within a system dictated by a unique set of

transmission factors. Many parasites must reach a certain population

size within the host to be successfully transmitted, while in certain

systems, sacrifice of one host facilitates transmission to the next

host (i.e. interspecies transmission). The inclusiveness of the

equilibrium model gives it great potential for accurate predictability

of a broad range of parasite-host interactions.

CONCLUSION

Traditional assumptions about the factors determining parasitic

strategy have been largely apocryphal, ignoring contradictory evidence

(Esch and Fernandez 1993). Equilibrium models synthesize the temporal

(i.e. evolutionary) factors and spatial (i.e. transmission) factors

characteristic of parasite-host systems. Time is required to modulate

virulence, while spatial factors such as host density and transmission

strategy determine the direction of the modulation.

The development of an inclusive, accurate model has significance

beyond theoretical biology, given the threat to human populations

posed by pathogens such as HIV (Gibbons 1994). Mass extinctions such

as the Cretaceous event may have resulted from parasite-host

interaction (Bakker 1986), and sexual reproduction (i.e. recombination

of genes during meiosis) may have evolved to increase resistance to

parasites (Holmes 1993). Parasitism constitutes an immense, if not

universal, influence on the evolution of life, with far-reaching

paleological and phylogenetic implications. A model which synthesizes

the key factors determining parasitic virulence and can predict the

entire range of evolutionary outcomes is crucial to our understanding

of the history and future of species interaction.