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. 1985;63(2):387–398.

Recent advances in malaria parasite cultivation and their application to studies on host-parasite relationships: a review

P I Trigg
PMCID: PMC2536397  PMID: 3893779

Abstract

The continuous cultivation of the erythrocytic stages of Plasmodium falciparum was achieved in 1976 and techniques have now also been developed for continuous cultivation of these stages from P. knowlesi, P. fragile, P. inui, P. cynomolgi and P. berghei. The requisite conditions for successful cultivation are described. Gametes of certain isolates of P. falciparum can also now be produced in vitro and these are infective to mosquitos, leading to normal development of the parasite.

The successful cultivation in vitro of the exoerythrocytic stages of P. berghei and P. vivax was achieved in 1981 and 1983, respectively. These cultures give rise to infective merozoites.

There have been no significant advances in the in vitro cultivation of the sporogonic stages of malaria parasites for the last 15 years, although studies indicate that the in vitro cultivation of these stages from gamete to sporozoite stage is theoretically possible.

The application of cultivation techniques to the study of parasite epidemiology is discussed. To date the major epidemiological impact has related to their use for measuring the incidence and spread of drug resistance. Applications to the study of the genetics of drug resistance, antigen production, development of tests for protective immunity, and drug development and screening are reviewed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alger N. E. In vitro development of Plasmodium berghei ookinetes. Nature. 1968 May 25;218(5143):774–774. doi: 10.1038/218774a0. [DOI] [PubMed] [Google Scholar]
  2. Bass C. C., Johns F. M. THE CULTIVATION OF MALARIAL PLASMODIA (PLASMODIUM VIVAX AND PLASMODIUM FALCIPARUM) IN VITRO. J Exp Med. 1912 Oct 1;16(4):567–579. doi: 10.1084/jem.16.4.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell C. C., Collins W. E., Nguyen-Dinh P., Barber A., Broderson J. R. Plasmodium falciparum gametocytes from culture in vitro develop to sporozoites that are infectious to primates. Science. 1982 Sep 10;217(4564):1048–1050. doi: 10.1126/science.7051285. [DOI] [PubMed] [Google Scholar]
  4. Capps T. C., Jensen J. B. Storage requirements for erythrocytes used to culture Plasmodium falciparum. J Parasitol. 1983 Feb;69(1):158–162. [PubMed] [Google Scholar]
  5. Carter R., Beach R. F. Gametogenesis in culture by gametocytes of Plasmodium falciparum. Nature. 1977 Nov 17;270(5634):240–241. doi: 10.1038/270240a0. [DOI] [PubMed] [Google Scholar]
  6. Carter R., Miller L. H. Evidence for environmental modulation of gametocytogenesis in Plasmodium falciparum in continuous culture. Bull World Health Organ. 1979;57 (Suppl 1):37–52. [PMC free article] [PubMed] [Google Scholar]
  7. Carter R., Voller A. The distribution of enzyme variation in populations of Plasmodium falciparum in Africa. Trans R Soc Trop Med Hyg. 1975;69(4):371–376. doi: 10.1016/0035-9203(75)90191-1. [DOI] [PubMed] [Google Scholar]
  8. Chowdhuri A. N., Chowdhury D. S., Regis M. L. Simultaneous propagation of P. malariae and P. falciparum in a continuous culture. Indian J Med Res. 1979 Dec;70 (Suppl):72–78. [PubMed] [Google Scholar]
  9. Desjardins R. E., Canfield C. J., Haynes J. D., Chulay J. D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother. 1979 Dec;16(6):710–718. doi: 10.1128/aac.16.6.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Divo A. A., Jensen J. B. Studies on serum requirements for the cultivation of Plasmodium falciparum. 1. Animal sera. Bull World Health Organ. 1982;60(4):565–569. [PMC free article] [PubMed] [Google Scholar]
  11. Divo A. A., Jensen J. B. Studies on serum requirements for the cultivation of Plasmodium falciparum. 2. Medium enrichment. Bull World Health Organ. 1982;60(4):571–575. [PMC free article] [PubMed] [Google Scholar]
  12. Draper C. C., Brubaker G., Geser A., Kilimali V. A., Wernsdorfer W. H. Serial studies on the evolution of chloroquine resistance in an area of East Africa receiving intermittent malaria chemosuppression. Bull World Health Organ. 1985;63(1):109–118. [PMC free article] [PubMed] [Google Scholar]
  13. Haynes J. D., Diggs C. L., Hines F. A., Desjardins R. E. Culture of human malaria parasites Plasmodium falciparum. Nature. 1976 Oct 28;263(5580):767–769. doi: 10.1038/263767a0. [DOI] [PubMed] [Google Scholar]
  14. Hollingdale M. R., Leef J. L., McCullough M., Beaudoin R. L. In vitro cultivation of the exoerythrocytic stage of Plasmodium berghei from sporozoites. Science. 1981 Aug 28;213(4511):1021–1022. doi: 10.1126/science.7022652. [DOI] [PubMed] [Google Scholar]
  15. Ifediba T., Vanderberg J. P. Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature. 1981 Nov 26;294(5839):364–366. doi: 10.1038/294364a0. [DOI] [PubMed] [Google Scholar]
  16. Ifediba T., Vanderberg J. P. Peptones and calf serum as a replacement for human serum in the cultivation of Plasmodium falciparum. J Parasitol. 1980 Apr;66(2):236–239. [PubMed] [Google Scholar]
  17. Jensen J. B., Boland M. T., Hayes M., Akood M. A. Plasmodium falciparum: rapid assay for in vitro inhibition due to human serum from residents of malarious areas. Exp Parasitol. 1982 Dec;54(3):416–424. doi: 10.1016/0014-4894(82)90051-0. [DOI] [PubMed] [Google Scholar]
  18. Jensen J. B., Boland M. T., Hayes M., Akood M. A. Plasmodium falciparum: rapid assay for in vitro inhibition due to human serum from residents of malarious areas. Exp Parasitol. 1982 Dec;54(3):416–424. doi: 10.1016/0014-4894(82)90051-0. [DOI] [PubMed] [Google Scholar]
  19. Jensen J. B., Trager W., Doherty J. Plasmodium falciparum: continuous cultivation in a semiautomated apparatus. Exp Parasitol. 1979 Aug;48(1):36–41. doi: 10.1016/0014-4894(79)90052-3. [DOI] [PubMed] [Google Scholar]
  20. Jensen J. B., Trager W. Plasmodium falciparum in culture: use of outdated erthrocytes and description of the candle jar method. J Parasitol. 1977 Oct;63(5):883–886. [PubMed] [Google Scholar]
  21. Lambros C., Vanderberg J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979 Jun;65(3):418–420. [PubMed] [Google Scholar]
  22. Lamont G., Saul A., Kidson C. Plasmodium falciparum: assay of invasion of erythrocytes. Exp Parasitol. 1981 Feb;51(1):74–79. doi: 10.1016/0014-4894(81)90043-6. [DOI] [PubMed] [Google Scholar]
  23. Langreth S. G., Reese R. T., Motyl M. R., Trager W. Plasmodium falciparum: loss of knobs on the infected erythrocyte surface after long-term cultivation. Exp Parasitol. 1979 Oct;48(2):213–219. doi: 10.1016/0014-4894(79)90101-2. [DOI] [PubMed] [Google Scholar]
  24. Mazier D., Landau I., Druilhe P., Miltgen F., Guguen-Guillouzo C., Baccam D., Baxter J., Chigot J. P., Gentilini M. Cultivation of the liver forms of Plasmodium vivax in human hepatocytes. 1984 Jan 26-Feb 1Nature. 307(5949):367–369. doi: 10.1038/307367a0. [DOI] [PubMed] [Google Scholar]
  25. Motyl M. R., Reese R. T. Plasmodium falciparum: comparison of in vitro growth of knobby and knobless isolates. Am J Trop Med Hyg. 1983 Mar;32(2):226–230. doi: 10.4269/ajtmh.1983.32.226. [DOI] [PubMed] [Google Scholar]
  26. Mrema J. E., Campbell G. H., Miranda R., Jaramillo A. L., Rieckmann K. H. Concentration and separation of erythrocytes infected with Plasmodium falciparum by gradient centrifugation. Bull World Health Organ. 1979;57(1):133–138. [PMC free article] [PubMed] [Google Scholar]
  27. Nguyen-Dinh P., Campbell C. C., Collins W. E. Cultivation in vitro of the quartan malaria parasite Plasmodium inui. Science. 1980 Sep 12;209(4462):1249–1251. doi: 10.1126/science.6773146. [DOI] [PubMed] [Google Scholar]
  28. Nguyen-Dinh P., Gardner A. L., Campbell C. C., Skinner J. C., Collins W. E. Cultivation in vitro of the vivax-type malaria parasite Plasmodium cynomolgi. Science. 1981 Jun 5;212(4499):1146–1148. doi: 10.1126/science.7233207. [DOI] [PubMed] [Google Scholar]
  29. Nguyen-Dinh P., Hobbs J. H., Campbell C. C. Assessment of chloroquine sensitivity of Plasmodium falciparum in Choluteca, Honduras. Bull World Health Organ. 1981;59(4):641–646. [PMC free article] [PubMed] [Google Scholar]
  30. Nguyen-Dinh P., Spencer H. C., Chemangey-Masaba S., Churchill F. C. Susceptibility of Plasmodium falciparum to pyrimethamine and sulfadoxine/pyrimethamine in Kisumu, Kenya. Lancet. 1982 Apr 10;1(8276):823–825. doi: 10.1016/s0140-6736(82)91873-6. [DOI] [PubMed] [Google Scholar]
  31. Palmer K. L., Hui G. S., Siddiqui W. A., Palmer E. L. A large-scale in vitro production system for Plasmodium falciparum. J Parasitol. 1982 Dec;68(6):1180–1183. [PubMed] [Google Scholar]
  32. Pasvol G., Wainscoat J. S., Weatherall D. J. Erythrocytes deficiency in glycophorin resist invasion by the malarial parasite Plasmodium falciparum. Nature. 1982 May 6;297(5861):64–66. doi: 10.1038/297064a0. [DOI] [PubMed] [Google Scholar]
  33. Rieckmann K. H., Campbell G. H., Sax L. J., Mrema J. E. Drug sensitivity of plasmodium falciparum. An in-vitro microtechnique. Lancet. 1978 Jan 7;1(8054):22–23. doi: 10.1016/s0140-6736(78)90365-3. [DOI] [PubMed] [Google Scholar]
  34. Rieckmann K. H. Visual in-vitro test for determining the drug sensitivity of Plasmodium falciparum. Lancet. 1982 Jun 12;1(8285):1333–1335. doi: 10.1016/s0140-6736(82)92403-5. [DOI] [PubMed] [Google Scholar]
  35. Rosales-Ronquillo M. C., Silverman P. H. In vitro ookinete development of the rodent malarial parasite, Plasmodium berghei. J Parasitol. 1974 Oct;60(5):819–824. [PubMed] [Google Scholar]
  36. Rosario V. Cloning of naturally occurring mixed infections of malaria parasites. Science. 1981 May 29;212(4498):1037–1038. doi: 10.1126/science.7015505. [DOI] [PubMed] [Google Scholar]
  37. Ross C., Jensen B. Patient Profile: Inuvik General Hospital and Four Regional Nursing Stations, NWT. Can Fam Physician. 1980 Jan;26:129–136. [PMC free article] [PubMed] [Google Scholar]
  38. Sax L. J., Rieckmann K. H. Use of rabbit serum in the cultivation of Plasmodium falciparum. J Parasitol. 1980 Aug;66(4):621–624. [PubMed] [Google Scholar]
  39. Shapiro M., Espinal-Tejada C., Nussenzweig R. S. Evaluation of a method for in vitro ookinete development of the rodent malarial parasite, Plasmodium berghei. J Parasitol. 1975 Dec;61(6):1105–1106. [PubMed] [Google Scholar]
  40. Sinden R. E., Smith J. Culture of the liver stages (exoerythrocytic schizonts) of rodent malaria parasites from sporozoites in vitro. Trans R Soc Trop Med Hyg. 1980;74(1):134–136. doi: 10.1016/0035-9203(80)90033-4. [DOI] [PubMed] [Google Scholar]
  41. Strome C. P., De Santis P. L., Beaudoin R. L. The cultivation of the exoerythrocytic stages of Plasmodium berghei from sporozoites. In Vitro. 1979 Jul;15(7):531–536. doi: 10.1007/BF02618155. [DOI] [PubMed] [Google Scholar]
  42. Thaithong S. Clones of different sensitivities in drug-resistant isolates of Plasmodium falciparum. Bull World Health Organ. 1983;61(4):709–712. [PMC free article] [PubMed] [Google Scholar]
  43. Trager W. A new method for intraerythrocytic cultivation of malaria parasites (Plasmodium coatneyi and P. falciparum). J Protozool. 1971 May;18(2):239–242. doi: 10.1111/j.1550-7408.1971.tb03314.x. [DOI] [PubMed] [Google Scholar]
  44. Trager W., Jenson J. B. Cultivation of malarial parasites. Nature. 1978 Jun 22;273(5664):621–622. doi: 10.1038/273621a0. [DOI] [PubMed] [Google Scholar]
  45. Udeinya I. J., Miller L. H., McGregor I. A., Jensen J. B. Plasmodium falciparum strain-specific antibody blocks binding of infected erythrocytes to amelanotic melanoma cells. Nature. 1983 Jun 2;303(5916):429–431. doi: 10.1038/303429a0. [DOI] [PubMed] [Google Scholar]
  46. Vanderberg J. P., Weiss M. M., Mack S. R. In vitro cultivation of the sporogonic stages of Plasmodium: a review. Bull World Health Organ. 1977;55(2-3):377–392. [PMC free article] [PubMed] [Google Scholar]
  47. Weiss M. M., Vanderberg J. P. Studies on Plasmodium ookinetes: II. In vitro formation of Plasmodium berghei ookinetes. J Parasitol. 1977 Oct;63(5):932–934. [PubMed] [Google Scholar]
  48. Wernsdorfer W. H. Field evaluation of drug resistance in malaria. In vitro micro-test. Acta Trop. 1980 Sep;37(3):222–227. [PubMed] [Google Scholar]
  49. Willet G. P., Canfield C. J. Plasmodium falciparum: continuous cultivation of erythrocyte stages in plasma-free culture medium. Exp Parasitol. 1984 Feb;57(1):76–80. doi: 10.1016/0014-4894(84)90065-1. [DOI] [PubMed] [Google Scholar]
  50. Wilson R. J., Phillips R. S. Method to test inhibitory antibodies in human sera to wild populations of Plasmodium falciparum. Nature. 1976 Sep 9;263(5573):132–134. doi: 10.1038/263132a0. [DOI] [PubMed] [Google Scholar]
  51. Zolg J. W., MacLeod A. J., Dickson I. H., Scaife J. G. Plasmodium falciparum: modifications of the in vitro culture conditions improving parasitic yields. J Parasitol. 1982 Dec;68(6):1072–1080. [PubMed] [Google Scholar]

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