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Proceedings of the Royal Society B: Biological Sciences logoLink to Proceedings of the Royal Society B: Biological Sciences
. 2002 Jun 22;269(1497):1217–1224. doi: 10.1098/rspb.2002.2023

Genetic and environmental determinants of malaria parasite virulence in mosquitoes.

H M Ferguson 1, A F Read 1
PMCID: PMC1691016  PMID: 12065037

Abstract

Models of malaria epidemiology and evolution are frequently based on the assumption that vector-parasitic associations are benign. Implicit in this assumption is the supposition that all Plasmodium parasites have an equal and neutral effect on vector survival, and thus that there is no parasite genetic variation for vector virulence. While some data support the assumption of avirulence, there has been no examination of the impact of parasite genetic diversity. We conducted a laboratory study with the rodent malaria parasite, Plasmodium chabaudi and the vector, Anopheles stephensi, to determine whether mosquito mortality varied with parasite genotype (CR and ER clones), infection diversity (single versus mixed genotype) and nutrient availability. Vector mortality varied significantly between parasite genotypes, but the rank order of virulence depended on environmental conditions. In standard conditions, mixed genotype infections were the most virulent but when glucose water was limited, mortality was highest in mosquitoes infected with CR. These genotype-by-environment interactions were repeatable across two experiments and could not be explained by variation in anaemia, gametocytaemia, blood meal size, mosquito body size, infection rate or oocyst burden. Variation in the genetic and environmental determinants of virulence may explain conflicting accounts of Plasmodium pathogenicity to mosquitoes in the malaria literature.

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Selected References

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  1. Anderson R. A., Knols B. G., Koella J. C. Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l. Parasitology. 2000 Apr;120(Pt 4):329–333. doi: 10.1017/s0031182099005570. [DOI] [PubMed] [Google Scholar]
  2. Anderson R. A., Koella J. C., Hurd H. The effect of Plasmodium yoelii nigeriensis infection on the feeding persistence of Anopheles stephensi Liston throughout the sporogonic cycle. Proc Biol Sci. 1999 Sep 7;266(1430):1729–1733. doi: 10.1098/rspb.1999.0839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beier J. C., Perkins P. V., Koros J. K., Onyango F. K., Gargan T. P., Wirtz R. A., Koech D. K., Roberts C. R. Malaria sporozoite detection by dissection and ELISA to assess infectivity of afrotropical Anopheles (Diptera: Culicidae). J Med Entomol. 1990 May;27(3):377–384. doi: 10.1093/jmedent/27.3.377. [DOI] [PubMed] [Google Scholar]
  4. Carlson J., Helmby H., Hill A. V., Brewster D., Greenwood B. M., Wahlgren M. Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet. 1990 Dec 15;336(8729):1457–1460. doi: 10.1016/0140-6736(90)93174-n. [DOI] [PubMed] [Google Scholar]
  5. Chao L., Hanley K. A., Burch C. L., Dahlberg C., Turner P. E. Kin selection and parasite evolution: higher and lower virulence with hard and soft selection. Q Rev Biol. 2000 Sep;75(3):261–275. doi: 10.1086/393499. [DOI] [PubMed] [Google Scholar]
  6. Chege G. M., Beier J. C. Blood acquisition and processing by three Anopheles (Diptera: Culicidae) species with different innate susceptibilities to Plasmodium falciparum. J Med Entomol. 1998 May;35(3):319–323. doi: 10.1093/jmedent/35.3.319. [DOI] [PubMed] [Google Scholar]
  7. Chege G. M., Beier J. C. Effect of Plasmodium falciparum on the survival of naturally infected afrotropical Anopheles (Diptera: Culicidae). J Med Entomol. 1990 Jul;27(4):454–458. doi: 10.1093/jmedent/27.4.454. [DOI] [PubMed] [Google Scholar]
  8. Chen Q., Barragan A., Fernandez V., Sundström A., Schlichtherle M., Sahlén A., Carlson J., Datta S., Wahlgren M. Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. J Exp Med. 1998 Jan 5;187(1):15–23. doi: 10.1084/jem.187.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chotivanich K., Udomsangpetch R., Simpson J. A., Newton P., Pukrittayakamee S., Looareesuwan S., White N. J. Parasite multiplication potential and the severity of Falciparum malaria. J Infect Dis. 2000 Mar;181(3):1206–1209. doi: 10.1086/315353. [DOI] [PubMed] [Google Scholar]
  10. Ferguson Heather M., Read Andrew F. Why is the effect of malaria parasites on mosquito survival still unresolved? Trends Parasitol. 2002 Jun;18(6):256–261. doi: 10.1016/s1471-4922(02)02281-x. [DOI] [PubMed] [Google Scholar]
  11. Foster W. A. Mosquito sugar feeding and reproductive energetics. Annu Rev Entomol. 1995;40:443–474. doi: 10.1146/annurev.en.40.010195.002303. [DOI] [PubMed] [Google Scholar]
  12. Frank S. A. A kin selection model for the evolution of virulence. Proc Biol Sci. 1992 Dec 22;250(1329):195–197. doi: 10.1098/rspb.1992.0149. [DOI] [PubMed] [Google Scholar]
  13. Frank S. A. Models of parasite virulence. Q Rev Biol. 1996 Mar;71(1):37–78. doi: 10.1086/419267. [DOI] [PubMed] [Google Scholar]
  14. Freier J. E., Friedman S. Effect of Plasmodium gallinaceum infection on the mortality and body weight of Aedes aegypti (Diptera: Culicidae). J Med Entomol. 1987 Jan;24(1):6–10. doi: 10.1093/jmedent/24.1.6. [DOI] [PubMed] [Google Scholar]
  15. Gad A. M., Maier W. A., Piekarski G. Pathology of Anopheles stephensi after infection with Plasmodium berghei berghei. I. Mortality rate. Z Parasitenkd. 1979 Dec 1;60(3):249–261. doi: 10.1007/BF00929172. [DOI] [PubMed] [Google Scholar]
  16. Gamage-Mendis A. C., Rajakaruna J., Weerasinghe S., Mendis C., Carter R., Mendis K. N. Infectivity of Plasmodium vivax and P. falciparum to Anopheles tessellatus; relationship between oocyst and sporozoite development. Trans R Soc Trop Med Hyg. 1993 Jan-Feb;87(1):3–6. doi: 10.1016/0035-9203(93)90396-8. [DOI] [PubMed] [Google Scholar]
  17. Gary R. E., Jr, Foster W. A. Effects of available sugar on the reproductive fitness and vectorial capacity of the malaria vector Anopheles gambiae (Diptera: Culicidae). J Med Entomol. 2001 Jan;38(1):22–28. doi: 10.1603/0022-2585-38.1.22. [DOI] [PubMed] [Google Scholar]
  18. Hargreaves J., Yoeli M., Nussenzweig R. S. Immunological studies in rodent malaria. I: Protective immunity induced in mice by mild strains of Plasmodium berghei yoelii against a virulent and fatal line of this plasmodium. Ann Trop Med Parasitol. 1975 Sep;69(3):289–299. [PubMed] [Google Scholar]
  19. Hogg J. C., Hurd H. Malaria-induced reduction of fecundity during the first gonotrophic cycle of Anopheles stephensi mosquitoes. Med Vet Entomol. 1995 Apr;9(2):176–180. doi: 10.1111/j.1365-2915.1995.tb00175.x. [DOI] [PubMed] [Google Scholar]
  20. Hogg J. C., Hurd H. The effects of natural Plasmodium falciparum infection on the fecundity and mortality of Anopheles gambiae s. l. in north east Tanzania. Parasitology. 1997 Apr;114(Pt 4):325–331. doi: 10.1017/s0031182096008542. [DOI] [PubMed] [Google Scholar]
  21. Klein T. A., Harrison B. A., Grove J. S., Dixon S. V., Andre R. G. Correlation of survival rates of Anopheles dirus A (Diptera: Culicidae) with different infection densities of Plasmodium cynomolgi. Bull World Health Organ. 1986;64(6):901–907. [PMC free article] [PubMed] [Google Scholar]
  22. Koella J. C. An evolutionary view of the interactions between anopheline mosquitoes and malaria parasites. Microbes Infect. 1999 Apr;1(4):303–308. doi: 10.1016/s1286-4579(99)80026-4. [DOI] [PubMed] [Google Scholar]
  23. Koella J. C., Sørensen F. L., Anderson R. A. The malaria parasite, Plasmodium falciparum, increases the frequency of multiple feeding of its mosquito vector, Anopheles gambiae. Proc Biol Sci. 1998 May 7;265(1398):763–768. doi: 10.1098/rspb.1998.0358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lines J. D., Wilkes T. J., Lyimo E. O. Human malaria infectiousness measured by age-specific sporozoite rates in Anopheles gambiae in Tanzania. Parasitology. 1991 Apr;102(Pt 2):167–177. doi: 10.1017/s0031182000062454. [DOI] [PubMed] [Google Scholar]
  25. Lombardi S., Esposito F., Zavala F., Lamizana L., Rossi P., Sabatinelli G., Nussenzweig R. S., Coluzzi M. Detection and anatomical localization of Plasmodium falciparum circumsporozoite protein and sporozoites in the afrotropical malaria vector Anopheles gambiae s.l. Am J Trop Med Hyg. 1987 Nov;37(3):491–494. doi: 10.4269/ajtmh.1987.37.491. [DOI] [PubMed] [Google Scholar]
  26. Lyimo E. O., Koella J. C. Relationship between body size of adult Anopheles gambiae s.l. and infection with the malaria parasite Plasmodium falciparum. Parasitology. 1992 Apr;104(Pt 2):233–237. doi: 10.1017/s0031182000061667. [DOI] [PubMed] [Google Scholar]
  27. Mackinnon M. J., Read A. F. Selection for high and low virulence in the malaria parasite Plasmodium chabaudi. Proc Biol Sci. 1999 Apr 7;266(1420):741–748. doi: 10.1098/rspb.1999.0699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Maier W. A., Becker-Feldman H., Seitz H. M. Pathology of malaria-infected mosquitoes. Parasitol Today. 1987 Jul;3(7):216–218. doi: 10.1016/0169-4758(87)90063-9. [DOI] [PubMed] [Google Scholar]
  29. Maier W. A. Uber die Mortalität von Culex pipens fatigans nach Infektion mit Plasmodium cathemerium. Z Parasitenkd. 1973 Mar 15;41(1):11–28. doi: 10.1007/BF00329627. [DOI] [PubMed] [Google Scholar]
  30. Moret Y., Schmid-Hempel P. Survival for immunity: the price of immune system activation for bumblebee workers. Science. 2000 Nov 10;290(5494):1166–1168. doi: 10.1126/science.290.5494.1166. [DOI] [PubMed] [Google Scholar]
  31. Ponnudurai T., Lensen A. H., van Gemert G. J., Bolmer M., van Belkum A., van Eerd P., Mons B. Large-scale production of Plasmodium vivax sporozoites. Parasitology. 1990 Dec;101(Pt 3):317–320. doi: 10.1017/s0031182000060492. [DOI] [PubMed] [Google Scholar]
  32. Read A. F., Taylor L. H. The ecology of genetically diverse infections. Science. 2001 May 11;292(5519):1099–1102. doi: 10.1126/science.1059410. [DOI] [PubMed] [Google Scholar]
  33. Robert V., Verhave J. P., Carnevale P. Plasmodium falciparum infection does not increase the precocious mortality rate of Anopheles gambiae. Trans R Soc Trop Med Hyg. 1990 May-Jun;84(3):346–347. doi: 10.1016/0035-9203(90)90309-3. [DOI] [PubMed] [Google Scholar]
  34. Rowe J. A., Moulds J. M., Newbold C. I., Miller L. H. P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1. Nature. 1997 Jul 17;388(6639):292–295. doi: 10.1038/40888. [DOI] [PubMed] [Google Scholar]
  35. Sasaki A., Iwasa Y. Optimal growth schedule of pathogens within a host: switching between lytic and latent cycles. Theor Popul Biol. 1991 Apr;39(2):201–239. doi: 10.1016/0040-5809(91)90036-f. [DOI] [PubMed] [Google Scholar]
  36. Seitz H. M., Maier W. A., Rottok M., Becker-Feldmann H. Concomitant infections of Anopheles stephensi with Plasmodium berghei and Serratia marcescens: additive detrimental effects. Zentralbl Bakteriol Mikrobiol Hyg A. 1987 Aug;266(1-2):155–166. doi: 10.1016/s0176-6724(87)80029-9. [DOI] [PubMed] [Google Scholar]
  37. Straif S. C., Beier J. C. Effects of sugar availability on the blood-feeding behavior of Anopheles gambiae (Diptera:Culicidae). J Med Entomol. 1996 Jul;33(4):608–612. doi: 10.1093/jmedent/33.4.608. [DOI] [PubMed] [Google Scholar]
  38. Taylor L. H., Walliker D., Read A. F. Mixed-genotype infections of the rodent malaria Plasmodium chabaudi are more infectious to mosquitoes than single-genotype infections. Parasitology. 1997 Aug;115(Pt 2):121–132. doi: 10.1017/s0031182097001145. [DOI] [PubMed] [Google Scholar]
  39. Vaughan J. A., Noden B. H., Beier J. C. Population dynamics of Plasmodium falciparum sporogony in laboratory-infected Anopheles gambiae. J Parasitol. 1992 Aug;78(4):716–724. [PubMed] [Google Scholar]
  40. Wekesa J. W., Copeland R. S., Mwangi R. W. Effect of Plasmodium falciparum on blood feeding behavior of naturally infected Anopheles mosquitoes in western Kenya. Am J Trop Med Hyg. 1992 Oct;47(4):484–488. doi: 10.4269/ajtmh.1992.47.484. [DOI] [PubMed] [Google Scholar]
  41. Yoeli M., Hargreaves B., Carter R., Walliker D. Sudden increase in virulence in a strain of Plasmodium berghei yoelii. Ann Trop Med Parasitol. 1975 Jun;69(2):173–178. doi: 10.1080/00034983.1975.11686998. [DOI] [PubMed] [Google Scholar]

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