Article ID: WMC002363 ISSN 2046-1690

Does Offer Benefit to the Parasite?

Corresponding Author: Dr. Fatik B Mandal, Associate Professor in Zoology, Bankura Christian College, College Road, Bankura, 722101 - India

Submitting Author: Dr. Fatik B Mandal, Associate Professor in Zoology, Bankura Christian College, College Road, Bankura, 722101 - India

Article ID: WMC002363 Article Type: Review articles Submitted on:22-Oct-2011, 11:12:34 PM GMT Published on: 25-Oct-2011, 12:44:37 PM GMT Article URL: http://www.webmedcentral.com/article_view/2363 Subject Categories:PARASITOLOGY Keywords:Parasite\'s Virulence, Mutation, Co-, Adaptive Theory, Host Resistance, Mode of Transmission How to cite the article:Mandal F B. Does Virulence Offer Benefit to the Parasite? . WebmedCentral PARASITOLOGY 2011;2(10):WMC002363 Source(s) of Funding: None

Competing Interests: None

WebmedCentral > Review articles Page 1 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

Does Virulence Offer Benefit to the Parasite?

Author(s): Mandal F B

Abstract resistance leading to the development of more virulent virus strains 6,7. Killing the host may be advantageous for parasites which are transmitted only from dead hosts 8. The Probability of producing virulent variants Parasites and hosts remain locked in a continuous increases with host population size, and crowding and struggle for survival. The co-evolutionary interactions co-mingling of the different host species 9. The between the hosts and parasites influence both the parasite-host relations naturally constitute a host and parasite. Parasite pathogenesis and host co-adaptive evolutionary dance along the defense act in a concert to shape the evolution of pathogenecity threshold, which is likely to be crossed virulence. There are various theories on the evolution due to anthropogenic disturbances 10. With this of virulence in parasite. Host mortality, host resistance, summary of background of our understanding, the host recovery, mutation, co infection, super infection, present communication aims to sum up the topic of host heterogeneity, and mode of transmission have parasitic virulence in the light of modern evolutionary been described for explaining the virulence in parasite. research. The evolution of parasite virulence focuses on the tradeoff between costs and benefits of the parasite Virulence of parasite from the host exploitation and appears to be satisfactory. The interaction between the hosts and parasites is multidimensional, dynamic and Virulence is the reduction in host’s fitness due to exceedingly complex. A number of factors perhaps act parasite infection 11 which is proportional to reduction to shape the level of parasite virulence. Generally, in the reproductive success of the infected host. This virulence is not beneficial to most of the parasites. is not in the parasites interest to severely damage or Virulence attains a maximum level due to the mutation kills its host as this affects the parasite’s fitness. A which is induced by the changing environment. A weak host is the easier prey for parasites than a thorough understanding of pathogenesis including a strong one. Evolution leads to an increase or decrease complete inventory of spatial and temporal expression in virulence, depending on the circumstances 12 of genes by both hosts and parasites, from the time of .Virulence is indicated by the mortality of the infected exposure to the final resolution of infection, would hosts, the average life-span of infected hosts, and the contribute a lot in our understanding of evolution of lethal dose50, LD50. In avirulent parasite, the infected parasite’s virulence. host does not die. Evolutionary change of parasite Introduction occurs due to change in micro-environment provided by the host. Parasites with more opportunities for vertical transmission and reduced opportunities for often become less virulent 13. The survival of the parasite depends on the conditions The zoonotic transfer of a parasite from one host in which parasites grow and multiply1. Death of the species to another may be highly virulent in the new host often limits the evolutionary success of the host, as observed in 1918 influenza pandemic. Severe parasite. Successful microbes avoid extinction, virulence kills the host before the parasite’s multiply, and leave descendants 2. Myxoma virus transmission to new hosts. Less virulent parasite cause a mild disease in the American rabbit .Simian increases over time14. Immunodeficiency Virus (SIV) does not cause immunodeficiency in its natural hosts 3.Many Trade- off theory Orthomyxo-, Arena-, and Hantaviruses cause asymptomatic infection4. Some parasites are extremely virulent in the novel host. The virulence decline in The evolution of parasite virulence is based on a course of time as observed in smallpox, measles, and trade-off between the advantage of within-host 2. influenza in Indian populations In replication and the disadvantage of such replication on 5, Australian populations of European rabbits the host survival 15,16. Hypotheses on parasite virulence are initially introduced myxoma virus strain was lethal with the conventional wisdom, adaptive theory, and case mortality of > 99 percent. In subsequent years, non-adaptive theory. Changes in transmission rate the virulence was declined .Later, rabbits developed

WebmedCentral > Review articles Page 2 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

lead to changes in virulence suggesting the existence new hosts. This trade-off between the infection rate of underlying trade-off. Strong inhibition of host and the duration of infection determine the optimal immunity by the parasite reduces the parasite parasite infectivity and duration of infection. A shorter clearance rate from the host, increase the host’s death infection period is associated with high virulence of the rate and in such case the parasite tend to be relatively parasite. Parasite evolution with this trade-off is the more virulent. As the parasite gains the immediate backbone of the adaptive theory. Anderson and May 15 benefit of escaping before the subsequent proposed a theoretical framework for the evolution of consequences of immune manipulation 17, parasites. immuno-modulatory or escape mechanisms may be favoured in spite of their virulence. Some progress on Host mortality mechanistic coupling between transmission and virulence has been made 18. For example, transmission may occur through spores after host’s death. An increase in the parasite-independent host mortality Autographa californica, a nucleopolyhedro virus rate should lead to selection of parasites that kill their attacks caterpillars. After ingestion, the virus invades hosts rapidly and are more virulent 18. Shorter the midgut cells 19, replicates and spreads until more life-span of the host often leads to a shorter infection than 1010 polyhedra fill the host. Ultimately, the virus period that in turn selects for rapidly replicating produces chitinase and cathepsin that together parasite. A long host life-span leads to selection of breakdown the host cuticle. The host liquefies at death; slower replicating parasites with low virulence. These release the viruses which are taken up by other hosts. predictions have been tested with variable success 24. Many terminally killing have similar life In multiple infections , high virulence is evolve at low histories20. natural host mortality rate 25 as the long duration of infection increases the probability of an already In mammals; anthrax (Bacilus anthracis) is a case of infected host to be super-infected with a more virulent mechanistic coupling 21. In the late infection, bacterial parasite strain forcing the existing parasites to density in the host grows to high levels and the high become more virulent. Reduction in the mortality of concentration of anthrax lethal toxin knocks out the transmission stages allows parasites to compensate immune system by destroying the macrophages. for increased virulence and maintain infections in Anthrax oedema toxin causes the production of a high population previously too small to sustain them. amount of cAMP in host cells, which disrupts the flow Importantly, increase in the size of host population of ions and cellular functions leading to host death. usually leads to increase in the incidence of parasite Transmission occurs primarily by spores which are population26. released after the death of the host. B. cereus , although closely related to B. anthracis does not Host recovery/host resistance cause severe virulence 22 .B. cereus transmits through oral-faecal route, colonizes the intestine, and causes 23 diarrhoea .From an evolutionary perspective, In plants and invertebrates, host resistance is often mechanistic coupling between transmission and defined as inability of the parasite to infect the host 27. extreme virulence strongly shapes the life history of In vertebrates, host resistance is often the host ability 18. parasites In the first major transmission episode to mount an effective immune response to clear the parasite grows to maximum density and maximize the infection. An increase in the recovery rate should opportunities for successful transmission, select for more virulent parasites28 as a higher consequently severely damages the host, and the recovery rate leads to a shorter duration of infection chance of subsequent transmission rate is low. forcing parasites to evolve higher growth rate and The adaptive theory of virulence. Increased host resistance may select for high or low virulence depending on mechanisms of parasite evolution resistance 29. Imperfect vaccines increase host resistance and allow replication and transmission of parasites leading to evolution of parasites with low or Reproductive success of a parasite is sometimes high virulence depending on the vaccine 30 calculated by the number of newly infected hosts. A long period of infection is beneficial to the parasite. A Epidemic and endemic shorter infection period may be advantageous, if diseases compensated by an increase in the infection rate to

WebmedCentral > Review articles Page 3 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

parasite strains in the initial inoculums is the most likely mechanism by which multiple infections may In epidemic infections the number of susceptible hosts occur in acute infections. During chronic infections co-, is large and parasite strains infecting the hosts rapidly super infection and mutation may lead to increased 31 gain selective advantage . In endemic diseases there parasite diversity in infected hosts. 38. is always dearth of susceptible hosts, so parasites infecting the maximum number of hosts will have Host heterogeneity selective advantage. Thus, in endemic infections parasites maximize their basic reproductive number in case of directly transmitted diseases. Higher host Adaptive theory assumes that parasites evolve in densities and high rates of parasite transmission populations of identical hosts. Higher levels of host cause outbreaks of highly virulent parasites including heterogeneity would select for less virulent parasites 32,33. influenza, and HIV Host immunodeficiency .Spread of infections in host populations with low due to HIV infection may result from the within host, genetic diversity often results in high host moralities42. short-sighted evolution of the virus and may have Many parasites when serially pass in new genetically 34. nothing to do with the rate of virus transmission identical hosts evolve to increase their virulence. In Duration of HIV infection is inversely correlated with accord with this increase, virulence generally the virus density in plasma of infected hosts early in decreases when it is measured in the original host. An 35 the asymptomatic period of the infection . Viral load increase in virulence of serially pass parasites may be is positively correlated with the probability of simply due to strong selection for more rapid growth 36 heterosexual transmission of HIV . Such and not due to low genetic diversity of hosts 43. relationships indicate a positive correlation between Parasites causing acute infections in vertebrates HIV transmissibility and virulence for viral strains with evolve in the hosts that stochastically differ in their different set points. susceptibility to infection or their quality of the immune Mutation, co infection and response. In the absence of heterogeneity parasites evolve to an intermediate growth rate but kill no host super infection due to a high loss in total transmission when the parasite kills the host. When the level of host heterogeneity increases, the optimal level of virulence Adaptive theory assumes that only one parasite strain increases This is because in order to obtain the can occupy a given host. For example, Daphnia maximum total transmission, the parasite has to magna can be repeatedly infected with the same compromise between killing “susceptible” hosts and microsporidian parasite 37. Humans infected with obtaining high transmission from “resistant” hosts 44. malaria often harbor several different strains of the Thus, the analysis suggests that higher levels of parasite 38. Theoretical results suggest that competition stochastic heterogeneity should select for higher between different parasite stains within one host select optimal level of parasite virulence. for increased virulence because of the risk to share the host with a more virulent parasite strain. The Mode of transmission increase in the number of parasite strains occupying the same host may result from mutation 39 and co- or super infection 40. Mixed-clone infections of mice with Since host mobility is not required and may be even malaria parasite Plasmodium chabaudi result in higher deleterious for the transmission of vector-borne maximum weight loss of the host 38 that correlates well parasites, such parasites should on average be more with other measures of virulence in this experimental virulent than parasites that are transmitted directly and 45 system 41. Some observations of malaria infection in that require host mobility for transmission . Similar humans or trypanosome infection of bumblebee arguments are applied to water-borne infections suggest that single infections may be as virulent as causing diarrhea because they can spread from 46. mixed infections 38.During an acute infection, the immobilized hosts Assuming a positive correlation probability of super infecting an already infected host between parasite transmissibility and virulence for is very low because of the short duration of infection. directly transmitted and water-borne parasites, Ewald 47 Because of the short duration of infection, mutations and De Leo have found that parasites that can be are not likely to generate high diversity in the parasite transmitted directly through contact and indirectly population during the infection unless the mutation through environment evolve higher virulence than rate is extremely high. The presence of different parasites transmitted exclusively directly. Since

WebmedCentral > Review articles Page 4 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

indirect transmission is not affected by the correct since many host species may increase the rate immobilization, there is no decrease in transmission of their evolution by reproducing sexually 42. Clearly in rate with increasing virulence 47. Ewald has suggested the presence of parasites, hosts evolve to become that high longevity of parasites in the environment more resistant to the infection and this in turn may should select for high virulence, because longer affect parasite virulence. One good example is the survival in the environment relaxes the parasite need co-evolution of the myxoma virus and rabbits in for host and for transmission 33. Parasite longevity Australia, where as host’s evolved high levels of does not affect the optimal level of parasite virulence resistance, the virus evolved higher virulence 5. for endemic infections transmitted exclusively Parasites may evolve to high or low virulence indirectly 48. Assuming that there is no trade-off depending on particular properties of transmission and between the parasite longevity in the environment and host connectivity 53. its virulence, the authors found that parasite longevity affects only the R0 of the infection but not optimal Non-adaptive hypotheses of virulence. However, results suggest that it is very parasite virulence difficult to make any general predictions on whether there is any relationship between the route of transmission and optimal virulence unless specific In many cases, parasite virulence is not related to details of the infection are known. In contrast with parasite’s fitness and therefore should be considered parasites, transmitted horizontally, it has been argued as nonadaptive. In some cases, this is because such that vertically transmitted parasites should be less parasites infect hosts that are not normally transmitting virulent because in this case transmission of the the parasite to other hosts 2. Such accidental infection 48 parasite is linked to the survival of the host . Bull and or “spill-overs” may sometimes be lethal to the host, coworkers in a series of elegant experiments have although many harmless infections most likely occur shown that increasing opportunities for horizontal unnoticed 43. Infections of this type include soil bacteria transmission of a bacteriophage lead to selection of Clostridium tetani causing tetanus, and bacteria 13 more virulent viral stains . Finally, a comparative Clostridium botulinum causing botulism. Both study suggests that vertically transmitted lice are less parasites cause disease in humans by accident and virulent than horizontally transmitted mites while toxin production by these bacteria most likely has infecting the same host species, rock doves Columba evolved due to other reasons than to kill humans54. 50 livia While exclusively vertically transmitted parasites Similarly, hantaviruses, Niphavirus, and rabies may should evolve low virulence, even small rates of cause serious diseases but yet for neither of the horizontal transmission may be sufficient for infections there is detectable human to human maintenance of highly virulent parasites that are transmission of the parasite 4.It is possible, that such 51 transmitted vertically with high efficiency ., parasites spill-overs may with time evolve to begin spreading experiencing severe bottlenecks during vertical from human to human without the requirement for the transmission, may evolve lower virulence because of original hosts 55. In that case, virulence of such an 52. the reduced strength of intra-host competition Thus infection may evolve but how it will evolve would the amount of vertical transmission may indicate of depend on many biological details of the within-host how virulent a parasite is but it needs not be the dynamics and epidemiological spread of the parasite. general rule.Limited parasite dispersal favours lower Levin and Bull 34 have suggested that virulence of such parasite growth rates and, hence, reduced virulence infections may be a result of the short-sighted, because it decreases the direct benefit of producing within-host parasite evolution. Ebert42 argues that offspring, and increases the competition for hosts within-host evolution of highly virulent parasite strains experienced by both the focal individual and their may be the direct cost of having high mutation rate relatives. This demonstrates that reduced virulence required, for example, for evasion of the immune can be understood as an individual level adaptation by response. HIV persists for long periods of time in a the parasite to maximize its inclusive fitness, and given host and during that time it is faced with a 14 clarifies the links with virulence theory more generally constant pressure from the immune system. High Other factors mutation rate might be one way of avoiding the recognition by the immune response 56. A high mutation rate may have a cost of generating mutants that are able to end the infection by killing the host 57. Simple theory assumes that parasites evolve much An increase in the mutation rate of such parasites faster than their hosts, but this may not be entirely should lead to an increased probability of disease

WebmedCentral > Review articles Page 5 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

occurrence and to an increased total transmission evolution. 1999. CABI Publishing, New York, NY, USA. from hosts that have not developed the disease. 6.Merchant J, Kerr P, Simms N, Hood G, Pech R, Decrease of the mutation rate should reduce the total Robinson A. Monitoring the spread of myxoma virus in transmission of parasites. Alternative explanation for rabbit Oryctolagus cuniculus populations on the the N. meningitidis virulence has been suggested in a Southern tablelands of New South Wales, Australia. III. recent study by Ancel Mayers et al.58. In summary, Release, persistenceand rate of spread of an regardless of forces driving evolution of such parasites, identifiable strain of myxomavirus. 2003a. Epidemiol within-host evolution may be an important factor Infect; 130:135–47. affecting virulence of parasites which, when looked 7.Merchant J, Kerr P, Simms N, Robinson A. from a between-host viewpoint, may appear to be Monitoring the spread of myxoma virus in rabbit nonadaptive. Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia.I. Natural Conclusion occurrence of myxomatosis. Epidemiol Infect .2003b ;130:113–21. 8.Ebert D, Lipsitch M, Mangin K.The effect of parasites Parasites have short lives and populations in on host population density and extinction: comparisons to hosts. Parasites are probably going to Experimental with Daphnia and six adapt to most prevalent gene complexes of their host, microparasites. Am Nat.2000; 156:459–447 which means that there is, in general, a selective 9.Schrag SS, Winer P. Emerging infectious disease: advantage to rare alleles and recombination. This what are the relative roles of and principle states that since every improvement in one evolution.Trends Ecol. Evol. 1995; 10: 319-324. species will lead to a selective advantage for that 10.Anderson RM, May RM. Infectious diseases in species variation normally continuously lead to humans: dynamics and control. 1991.Oxford increase in fitness, in one species, or another. Since in University Press, Oxford, UK. general different species are co-evolving, 11.Ebert D and Herre E. The evolution of parasitic improvement in one species implies that it will get a diseases. Parasitology today .1996;12:96–101. competitive advantage on other species and thus, be 12.Mandal, FB.Textbook of animal behaviour. able to capture a larger share of resources available to 2010.PHI Learning Private Limited, New Delhi, India. all. This means that fitness increase in one ISBN: 978-81-203-4035-0 evolutionary system will tend to lead to fitness 13.Messenger SL, Molineux IJ, Bull JJ. Virulence decrease in another system 12.Evolution of virulence evolution in a virus obeys a tradeoff. Proc. R. Soc. should be viewed from broad biological, Lond. B Biol. Sci. 1999; 266: 397–404. epidemiological and clinical perspectives. Man made 14.Frank SA. Models of parasite virulence. Q.Rev. Biol. changes in the environment which facilitates zoonotic 1996; 71:37–78. transfer of parasites should be urgently addressed. 15Anderson RM, May RM. Coevolution of hosts and parasites. Parasitology.1982; 85:411-426. References 16.May RM, Anderson RM. Epidemiology and genetics in the coevolution of parasites and hosts. Proceedings of the Royal Society of London B, 1.Burnet M, White DO. Natural history of infectious Biological sciences .1983; 219:281-313. disease. Cambridge University Press, 1972, 17Perlman S, Dandekar AA. Immunopathogenesis of London, UK, Forth edition. Coronavirus infections: implications for SARS. Nat. 2.Mims CA., Nash A., Stephen J.Mims’ pathogenesis Rev. Microbiol. 2005; 5: 917–927. of infectious disease. Academic Press, 2001 18.Day T .Virulence evolution via host exploitation and London, UK, Fifth edition. toxin production in spore-producing pathogens. Ecol. 3.Chakrabarti L A, Lewin SR, Zhang L,Gettie A, Lett. 2002; 5: 471–476. Luckay A, Martin LN, Skulsky E, Ho DD, Cheng-Mayer 19.Szewczyk B, Hoyos-Carvajal L, Paluszek M, C, Marx PA. Normal T-cell turnover in sooty Skrzecz I & Lobo de Souza M mangabeys harboring active simian immunodeficiency .Baculoviruses-re-emerging biopesticides. Biotechnol. virus infection. 2000.J Virol ;74:1209–23. Adv. 2006; 24: 143–160. 4.Lednicky JA. Hantavirus: a short review.Arch Pathol 20.Ebert D, Weisser WW. Optimal killingfor obligate Lab Med . 2003; 127:30–35. killers: the evolution of life histories and virulence of 5.Fenner F, Fantini B. Biological control of vertebrate semelparous parasites. Proc R Soc LondB Biol Sci pests: the history of myxomatosis; an experiment in .1997; 264:985–91.

WebmedCentral > Review articles Page 6 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

21Abrami L, Reig N and Gisou van der Goot F. transmissionper coital act in monogamous, Anthrax toxin: the long and winding road that leads to heterosexual, HIV-1-discordant couples in Rakai, the kill. Trends Microbiol. 2005; 13: 72–78. Uganda. Lancet. 2001;357:1149–53. 22.Helgason E, Okstad OA, Caugant DA, Johansen 37.Ebert D. The ecological interactions between a HA, Fouet A, Mock M. Hegna I & Kolsto A B .Bacillus microsporidian parasite and its host Daphnia magna. J anthracis, Bacillus cereus and Bacillus Anim Ecol.1995; 64:361–369. thuringiensis—one species on the basis of genetic 38.Read AF, Mackinnon MJ, Anwar MA, Taylor LH. evidence. Appl. Environ. Microbiol. 2000; Kin-selection models as evolutionary explanations of 66:2627-2630 malaria, 2002 pp. 165–177. In: U Dieckmann, JAJ 23.Kotiranta A, Lounatmaa K, Haapasalo M. Metz, M W Sabelis, and K Sigmund (eds.), Adaptive Epidemiology and pathogenesis of Bacillus cereus dynamics of infectious disease: in pursuit of virulence infections. Microbes Infect. 2000; 2: 189–198. management. Oxford University Press. 24.Cooper V, Reiskind M, Miller J, Shelton K, Walther 39.Bonhoeffer S, Nowak M. Mutation and the evolution B, Elkinton J, Ewald P . Timing of transmission and the of virulence. Proc. R. Soc. Lond.B. 1994; 258:133–140. evolution of virulence of an insect virus. Proc R Soc 40.Leung B, Forbes MR. The evolution of virulence: a Lond B Biol Sci 2002; 269:1161–5. stochastic simulation model examining at 25.Gandon S, Jansen VA and van Baalen M.. Host life individual and population levels. Evolutionary Ecology history and the evolution of parasite virulence. .1998;12:165–177. Evolution.2001a; 55:1056–62. 41.Mackinnon MJ, Read AF. Genetic relationship 26.Mandal FB. Human Parasitology. 2011.PHI between parasite virulence and transmission in the Learning Private Limited, New Delhi, India. rodent malaria Plasmodium chabaudi.Evolution ISBN-978-81-203-4292-7 .1999;53:689–703. 27.Rolff J, Siva-Jothy M. Invertebrate ecological 42.Ebert D. The evolution and expression of parasite immunology. Science. 2003; 301:472–5. virulence, 1999. pp. 161–172. In S C Stearns (ed.), 28.Antia R, Lipsitch M. Mathematical models of Evolution in health and disease. Oxford parasite responses to host immune UniversityPress, New York, NY. defenses.Parasitology .1997; 115:S155–67. 43.Ebert D. Experimental evolution of 29.Gandon S, Michalakis Y. Evolution of parasite microparasites.Science.1998; 282:1432–5. virulence against qualitative or quantitative host 44.Ganusov VV, Bergstrom CT, Antia R. Within-host resistance. Proc R Soc Lond B Biol Sci 2000; population dynamics and the evolution of 267:985–90. microparasites in a heterogeneous host population. 30.Gandon S, Mackinnon MJ, Nee S, Read AF. Evolution. 2002; 52:213–23. Imperfect vaccines and the evolution of 45.Ewald P. Host-parasite relations, vectors, and the virulence. Nature.2001b; 414:751–6. evolution of disease severity. Ann Rev Ecol 31.Lenski RE, May RM . The evolution of virulence in System.1983;14:465–485. parasites and pathogens: reconciliation between two 46.Ewald P, Sussman J, Distler M, Libel C, Chammas competing hypotheses. J Theor Biol W, Dirita V, Salles C, Vicente A, Heitmann I , Cabello .1994;169:253–265. F. Evolutionary control of infectious disease: prospects 32.Ewald P . Transmission modes and the evolution of for vectorborne and waterborne pathogens. Mem Inst virulence with special reference to cholera, influenza Oswaldo Cruz .1998;93: 567-576 and aids. Human Nature.1991;2:1–30. 47.Ewald PW, De Leo G. Alternative transmission 33.Ewald P. Evolution of infectious disease. 1994. modes and the evolution of virulence, 2002 pp. 11–25. Oxford University Press, Oxford, NY, USA. In: U. Dieckmann JAJ. Metz M, Sabelis W and 34.Levin Band Bull J. Short-sighted evoluionand the Sigmund K (eds.), Adaptive dynamics of infectious virulence of pathogenic microorganisms.Trends in disease: in pirsuit of virulence Management.Oxford Microbiology .1994;2:76–81. University Press. 35.Goto Y, Nishimura Y, Baba K, Mizuno T, Endo Y, 48.Bonhoeffer S, Lenski RE, Ebert D. The curse of the Masuda K, Ohno K, Tsujimoto H. Association of pharaoh: the evolution of virulence in pathogens with plasma viral RNA load with prognosis in cats naturally long living propagules. Proc R Soc Lond B Biol Sci infected with feline immunodeficiency virus. J Virol. .1996;263:715–21. 2002; 76:10079–83. 49.Ewald P. Transmission modes and evolution of the 36.Gray RH, Wawer MJ, Brookmeyer R, Sewankambo parasitism-mutualism continuum. Ann N Y Acad Sci NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, .1987;503:295–306. vanCott T, Quinn TC. Probability of HIV-1 50.Clayton DH, Tompkins DM.. Ectoparasite virulence

WebmedCentral > Review articles Page 7 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

is linked to mode of transmission.Proc R Soc Lond B Biol Sci .1994;256:211–7. 51.Lipsitch M, Siller S, Nowak M. The evolution of virulence in pathogens with vertical and horizontal transmission. Evolution.1996; 50:1729–1741. 52.Bergstrom C, McElhany P, Real L.Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens. Proc Natl Acad Sci USA .1999;96:5095–100. 53.Read J, Keeling M. Disease evolutionon networks: the role of contact structure. Proc RSoc Lond B Biol Sci .2003;270:699–708. 54.Lipsitch M, Moxon R. Virulence and transmissibility of pathogens: what is the relationship? Trends Microbiol .1997; 5:31–37. 55.Antia R, Regoes R, Koella J, Bergstrom C. The role of evolution in the emergence of infectious diseases. Nature. 2003; 426:658–61. 56.Ploegh HL. Viral strategies of immune evasion.Science .1998;280:248–53. 57.Nowak MA, Anderson RM , McLean AR, Wolfs T, Goudsmit J, May RM .Antigenic diversity thresholds and the development of AIDS. Science 1991. 254: 963-369. 58.Ancel Meyer’s l, Levin BR, Richardson AR, Stojilikovic I. Epidemiology, hypermutation, within-host evolution and the virulence of neisseria meningitidis. Proc Roy Soc Lond B.2003; 270:1667–77.

WebmedCentral > Review articles Page 8 of 9 WMC002363 Downloaded from http://www.webmedcentral.com on 10-Jan-2012, 11:16:46 AM

Disclaimer

This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party. Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

WebmedCentral > Review articles Page 9 of 9