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. 1988;66(5):575–594.

Malaria diagnosis: Memorandum from a WHO Meeting*

PMCID: PMC2491192  PMID: 3061674

Abstract

This Memorandum reviews (1) the diagnostic requirements for malaria control within the primary health care system; (2) the current methods of malaria diagnosis used both in the clinic and in epidemiological studies; (3) the status of research on alternative methods to microscopy for the diagnosis of malaria; and (4) the application of new diagnostic methods in individual cases, in the community, and in the mosquito and their possible integration into existing epidemiological studies and control programmes. It also identifies priorities for the development and validation of new and reliable diagnostic techniques, and makes recommendations for the improvement, standardization, and utilization of current methodology.

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Selected References

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  1. Allison A. C., Eugui E. M. The role of cell-mediated immune responses in resistance to malaria, with special reference to oxidant stress. Annu Rev Immunol. 1983;1:361–392. doi: 10.1146/annurev.iy.01.040183.002045. [DOI] [PubMed] [Google Scholar]
  2. Avraham H., Golenser J., Bunnag D., Suntharasamai P., Tharavanij S., Harinasuta K. T., Sira D. T., Sulitzeanu D. Preliminary field trial of a radioimmunoassay for the diagnosis of malaria. Am J Trop Med Hyg. 1983 Jan;32(1):11–18. doi: 10.4269/ajtmh.1983.32.11. [DOI] [PubMed] [Google Scholar]
  3. Avraham H., Spira D. T., Gorsky Y., Sulitzeanu D. A solid-phase antibody binding-inhibition test, for the assay of Plasmodium berghei antigen and antibodies, using radioiodinated protein A. J Immunol Methods. 1980;32(2):151–155. doi: 10.1016/0022-1759(80)90068-x. [DOI] [PubMed] [Google Scholar]
  4. Barker R. H., Jr, Suebsaeng L., Rooney W., Alecrim G. C., Dourado H. V., Wirth D. F. Specific DNA probe for the diagnosis of Plasmodium falciparum malaria. Science. 1986 Mar 21;231(4744):1434–1436. doi: 10.1126/science.3513309. [DOI] [PubMed] [Google Scholar]
  5. Baudon D., Gazin P., Rea D., Carnevale P. A study of malaria morbidity in a rural area of Burkina Faso (West Africa) Trans R Soc Trop Med Hyg. 1985;79(2):283–284. doi: 10.1016/0035-9203(85)90361-x. [DOI] [PubMed] [Google Scholar]
  6. Baudon D., Roux J., Carnevale P., Rey J. L., Meyran M. B., Brandicourt O. Systematic chemotherapy of febrile cases: a substitute strategy for malaria control in rural areas of Africa. Trans R Soc Trop Med Hyg. 1986;80(1):164–164. doi: 10.1016/0035-9203(86)90225-7. [DOI] [PubMed] [Google Scholar]
  7. Beier J. C., Perkins P. V., Wirtz R. A., Whitmire R. E., Mugambi M., Hockmeyer W. T. Field evaluation of an enzyme-linked immunosorbent assay (ELISA) for Plasmodium falciparum sporozoite detection in anopheline mosquitoes from Kenya. Am J Trop Med Hyg. 1987 May;36(3):459–468. doi: 10.4269/ajtmh.1987.36.459. [DOI] [PubMed] [Google Scholar]
  8. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  9. Brown J., Greenwood B. M. Cellular and humoral inhibition of Plasmodium falciparum growth in vitro and recovery from acute malaria. Parasite Immunol. 1985 May;7(3):265–275. doi: 10.1111/j.1365-3024.1985.tb00075.x. [DOI] [PubMed] [Google Scholar]
  10. Brown T. J., Ercolani L., Ginsberg B. H. Properties and regulation of the T lymphocyte insulin receptor. J Recept Res. 1983;3(4):481–494. doi: 10.3109/10799898309041854. [DOI] [PubMed] [Google Scholar]
  11. Buesing M., Guerry P., Deisanti C., Franke E., Watt G., Rab M. A., Oster C. N., Burans J. P., Perine P. L. An oligonucleotide probe for detecting Plasmodium falciparum: an analysis of clinical specimens from six countries. J Infect Dis. 1987 Jun;155(6):1315–1318. doi: 10.1093/infdis/155.6.1315. [DOI] [PubMed] [Google Scholar]
  12. Burkot T. R., Williams J. L., Schneider I. Identification of Plasmodium falciparum-infected mosquitoes by a double antibody enzyme-linked immunosorbent assay. Am J Trop Med Hyg. 1984 Sep;33(5):783–788. doi: 10.4269/ajtmh.1984.33.783. [DOI] [PubMed] [Google Scholar]
  13. Burkot T. R., Zavala F., Gwadz R. W., Collins F. H., Nussenzweig R. S., Roberts D. R. Identification of malaria-infected mosquitoes by a two-site enzyme-linked immunosorbent assay. Am J Trop Med Hyg. 1984 Mar;33(2):227–231. doi: 10.4269/ajtmh.1984.33.227. [DOI] [PubMed] [Google Scholar]
  14. Celada A., Cruchaud A., Perrin L. H. Assessment of immune phagocytosis of Plasmodium falciparum infected red blood cells by human monocytes and polymorphonuclear leukocytes. A method for visualizing infected red blood cells ingested by phagocytes. J Immunol Methods. 1983 Oct 14;63(2):263–271. doi: 10.1016/0022-1759(83)90430-1. [DOI] [PubMed] [Google Scholar]
  15. Cheung A., Leban J., Shaw A. R., Merkli B., Stocker J., Chizzolini C., Sander C., Perrin L. H. Immunization with synthetic peptides of a Plasmodium falciparum surface antigen induces antimerozoite antibodies. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8328–8332. doi: 10.1073/pnas.83.21.8328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Czerkinsky C., Nilsson L. A., Ouchterlony O., Tarkowski A., Gretzer C. Detection of single antibody-secreting cells generated after in vitro antigen-induced stimulation of human peripheral blood lymphocytes. Scand J Immunol. 1984 Jun;19(6):575–579. doi: 10.1111/j.1365-3083.1984.tb00968.x. [DOI] [PubMed] [Google Scholar]
  17. Del Giudice G., Engers H. D., Tougne C., Biro S. S., Weiss N., Verdini A. S., Pessi A., Degremont A. A., Freyvogel T. A., Lambert P. H. Antibodies to the repetitive epitope of Plasmodium falciparum circumsporozoite protein in a rural Tanzanian community: a longitudinal study of 132 children. Am J Trop Med Hyg. 1987 Mar;36(2):203–212. doi: 10.4269/ajtmh.1987.36.203. [DOI] [PubMed] [Google Scholar]
  18. Del Giudice G., Verdini A. S., Pinori M., Pessi A., Verhave J. P., Tougne C., Ivanoff B., Lambert P. H., Engers H. D. Detection of human antibodies against Plasmodium falciparum sporozoites using synthetic peptides. J Clin Microbiol. 1987 Jan;25(1):91–96. doi: 10.1128/jcm.25.1.91-96.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Druilhe P., Pradier O., Marc J. P., Miltgen F., Mazier D., Parent G. Levels of antibodies to Plasmodium falciparum sporozoite surface antigens reflect malaria transmission rates and are persistent in the absence of reinfection. Infect Immun. 1986 Aug;53(2):393–397. doi: 10.1128/iai.53.2.393-397.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Evans R. L., Faldetta T. J., Humphreys R. E., Pratt D. M., Yunis E. J., Schlossman S. F. Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens. J Exp Med. 1978 Nov 1;148(5):1440–1445. doi: 10.1084/jem.148.5.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fortier B., Delplace P., Dubremetz J. F., Ajana F., Vernes A. Enzyme immunoassay for detection of antigen in acute Plasmodium falciparum malaria. Eur J Clin Microbiol. 1987 Oct;6(5):596–598. doi: 10.1007/BF02014260. [DOI] [PubMed] [Google Scholar]
  22. Franzén L., Westin G., Shabo R., Aslund L., Perlmann H., Persson T., Wigzell H., Pettersson U. Analysis of clinical specimens by hybridisation with probe containing repetitive DNA from Plasmodium falciparum. A novel approach to malaria diagnosis. Lancet. 1984 Mar 10;1(8376):525–528. doi: 10.1016/s0140-6736(84)90929-2. [DOI] [PubMed] [Google Scholar]
  23. Gabra M. S., Grossiord D., Perrin L. H., Shaw A., Cheung A., McGregor I. A. Defined Plasmodium falciparum antigens in malaria serology. Bull World Health Organ. 1986;64(6):889–896. [PMC free article] [PubMed] [Google Scholar]
  24. Grau G. E., Fajardo L. F., Piguet P. F., Allet B., Lambert P. H., Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. doi: 10.1126/science.3306918. [DOI] [PubMed] [Google Scholar]
  25. Hoffman S. L., Oster C. N., Plowe C. V., Woollett G. R., Beier J. C., Chulay J. D., Wirtz R. A., Hollingdale M. R., Mugambi M. Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications. Science. 1987 Aug 7;237(4815):639–642. doi: 10.1126/science.3299709. [DOI] [PubMed] [Google Scholar]
  26. Hoffman S. L., Wistar R., Jr, Ballou W. R., Hollingdale M. R., Wirtz R. A., Schneider I., Marwoto H. A., Hockmeyer W. T. Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum. N Engl J Med. 1986 Sep 4;315(10):601–606. doi: 10.1056/NEJM198609043151001. [DOI] [PubMed] [Google Scholar]
  27. Hollingdale M. R., Nardin E. H., Tharavanij S., Schwartz A. L., Nussenzweig R. S. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J Immunol. 1984 Feb;132(2):909–913. [PubMed] [Google Scholar]
  28. Holmberg M., Björkman A., Franzén L., Aslund L., Lebbad M., Pettersson U., Wigzell H. Diagnosis of Plasmodium falciparum infection by spot hybridization assay: specificity, sensitivity, and field applicability. Bull World Health Organ. 1986;64(4):579–585. [PMC free article] [PubMed] [Google Scholar]
  29. Jensen J. B., Boland M. T., Akood M. Induction of crisis forms in cultured Plasmodium falciparum with human immune serum from Sudan. Science. 1982 Jun 11;216(4551):1230–1233. doi: 10.1126/science.7043736. [DOI] [PubMed] [Google Scholar]
  30. Judd W., Poodry C. A., Strominger J. L. Novel surface antigen expressed on dividing cells but absent from nondividing cells. J Exp Med. 1980 Nov 1;152(5):1430–1435. doi: 10.1084/jem.152.5.1430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kabilan L., Troye-Blomberg M., Patarroyo M. E., Björkman A., Perlmann P. Regulation of the immune response in Plasmodium falciparum malaria: IV. T cell dependent production of immunoglobulin and anti-P. falciparum antibodies in vitro. Clin Exp Immunol. 1987 May;68(2):288–297. [PMC free article] [PubMed] [Google Scholar]
  32. Landegren U. Measurement of cell numbers by means of the endogenous enzyme hexosaminidase. Applications to detection of lymphokines and cell surface antigens. J Immunol Methods. 1984 Mar 16;67(2):379–388. doi: 10.1016/0022-1759(84)90477-0. [DOI] [PubMed] [Google Scholar]
  33. Londner M. V., Rosen G., Sintov A., Spira D. T. The feasibility of a Dot enzyme-linked immunosorbent assay (Dot-ELISA) for the diagnosis of Plasmodium falciparum antigens and antibodies. Am J Trop Med Hyg. 1987 Mar;36(2):240–245. doi: 10.4269/ajtmh.1987.36.240. [DOI] [PubMed] [Google Scholar]
  34. Mackey L. J., McGregor I. A., Paounova N., Lambert P. H. Diagnosis of Plasmodium falciparum infection in man: detection of parasite antigens by ELISA. Bull World Health Organ. 1982;60(1):69–75. [PMC free article] [PubMed] [Google Scholar]
  35. Mackey L., Perrin L., Leemans E., Lambert P. H. The diagnosis of malaria infection using a solid-phase radioimmunoassay for the detection of malaria antigens. Application to the detection of Plasmodium berghei infection in mice. Parasitology. 1980 Feb;80(1):171–182. doi: 10.1017/s0031182000000639. [DOI] [PubMed] [Google Scholar]
  36. Mazier D., Mellouk S., Beaudoin R. L., Texier B., Druilhe P., Hockmeyer W., Trosper J., Paul C., Charoenvit Y., Young J. Effect of antibodies to recombinant and synthetic peptides on P. falciparum sporozoites in vitro. Science. 1986 Jan 10;231(4734):156–159. doi: 10.1126/science.3510455. [DOI] [PubMed] [Google Scholar]
  37. McCutchan T. F., de la Cruz V. F., Lal A. A., Gunderson J. H., Elwood H. J., Sogin M. L. Primary sequences of two small subunit ribosomal RNA genes from Plasmodium falciparum. Mol Biochem Parasitol. 1988 Feb;28(1):63–68. doi: 10.1016/0166-6851(88)90181-8. [DOI] [PubMed] [Google Scholar]
  38. McLaughlin G. L., Collins W. E., Campbell G. H. Comparison of genomic, plasmid, synthetic, and combined DNA probes for detecting Plasmodium falciparum DNA. J Clin Microbiol. 1987 May;25(5):791–795. doi: 10.1128/jcm.25.5.791-795.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McLaughlin G. L., Edlind T. D., Campbell G. H., Eller R. F., Ihler G. M. Detection of Plasmodium falciparum using a synthetic DNA probe. Am J Trop Med Hyg. 1985 Sep;34(5):837–840. doi: 10.4269/ajtmh.1985.34.837. [DOI] [PubMed] [Google Scholar]
  40. McLaughlin G. L., Ruth J. L., Jablonski E., Steketee R., Campbell G. H. Use of enzyme-linked synthetic DNA in diagnosis of falciparum malaria. Lancet. 1987 Mar 28;1(8535):714–716. doi: 10.1016/s0140-6736(87)90356-4. [DOI] [PubMed] [Google Scholar]
  41. Mendis K. N., Munesinghe Y. D., de Silva Y. N., Keragalla I., Carter R. Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. Infect Immun. 1987 Feb;55(2):369–372. doi: 10.1128/iai.55.2.369-372.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  43. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  44. Mucenski C. M., Guerry P., Buesing M., Szarfman A., Trosper J., Walliker D., Watt G., Sangalang R., Ranoa C. P., Tuazon M. Evaluation of a synthetic oligonucleotide probe for diagnosis of Plasmodium falciparum infections. Am J Trop Med Hyg. 1986 Sep;35(5):912–920. doi: 10.4269/ajtmh.1986.35.912. [DOI] [PubMed] [Google Scholar]
  45. Nardin E. H., Nussenzweig R. S., McGregor I. A., Bryan J. H. Antibodies to sporozoites: their frequent occurrence in individuals living in an area of hyperendemic malaria. Science. 1979 Nov 2;206(4418):597–599. doi: 10.1126/science.386511. [DOI] [PubMed] [Google Scholar]
  46. Ockenhouse C. F., Schulman S., Shear H. L. Induction of crisis forms in the human malaria parasite Plasmodium falciparum by gamma-interferon-activated, monocyte-derived macrophages. J Immunol. 1984 Sep;133(3):1601–1608. [PubMed] [Google Scholar]
  47. Perlmann H., Berzins K., Wahlgren M., Carlsson J., Björkman A., Patarroyo M. E., Perlmann P. Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum. J Exp Med. 1984 Jun 1;159(6):1686–1704. doi: 10.1084/jem.159.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Schloss J. A., Silflow C. D., Rosenbaum J. L. mRNA abundance changes during flagellar regeneration in Chlamydomonas reinhardtii. Mol Cell Biol. 1984 Mar;4(3):424–434. doi: 10.1128/mcb.4.3.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Takeuchi T., Schlossman S. F., Morimoto C. The T4 molecule differentially regulating the activation of subpopulations of T4+ cells. J Immunol. 1987 Aug 1;139(3):665–671. [PubMed] [Google Scholar]
  50. Troye-Blomberg M., Perlmann H., Patarroyo M. E., Perlmann P. Regulation of the immune response in Plasmodium falciparum malaria. II. Antigen specific proliferative responses in vitro. Clin Exp Immunol. 1983 Aug;53(2):345–353. [PMC free article] [PubMed] [Google Scholar]
  51. Verhave J. P., Leeuwenberg A. D., Ponnudurai T., Meuwissen J. H., van Druten J. A. The biotin-streptavidin system in a two-site ELISA for the detection of plasmodial sporozoite antigen in mosquitoes. Parasite Immunol. 1988 Jan;10(1):17–31. doi: 10.1111/j.1365-3024.1988.tb00200.x. [DOI] [PubMed] [Google Scholar]
  52. Vermeulen A. N., Ponnudurai T., Beckers P. J., Verhave J. P., Smits M. A., Meuwissen J. H. Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J Exp Med. 1985 Nov 1;162(5):1460–1476. doi: 10.1084/jem.162.5.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Wassom D. L., Johnson B. E., Sayles P. C. A filter immunoplaque assay for quantification of parasite-specific antibody producing cells. Parasitol Today. 1986 Aug;2(8):225–227. doi: 10.1016/0169-4758(86)90088-8. [DOI] [PubMed] [Google Scholar]
  54. Webster H. K., Boudreau E. F., Pang L. W., Permpanich B., Sookto P., Wirtz R. A. Development of immunity in natural Plasmodium falciparum malaria: antibodies to the falciparum sporozoite vaccine 1 antigen (R32tet32). J Clin Microbiol. 1987 Jun;25(6):1002–1008. doi: 10.1128/jcm.25.6.1002-1008.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Zavala F., Gwadz R. W., Collins F. H., Nussenzweig R. S., Nussenzweig V. Monoclonal antibodies to circumsporozoite proteins identify the species of malaria parasite in infected mosquitoes. Nature. 1982 Oct 21;299(5885):737–738. doi: 10.1038/299737a0. [DOI] [PubMed] [Google Scholar]
  56. Zavala F., Masuda A., Graves P. M., Nussenzweig V., Nussenzweig R. S. Ubiquity of the repetitive epitope of the CS protein in different isolates of human malaria parasites. J Immunol. 1985 Oct;135(4):2790–2793. [PubMed] [Google Scholar]
  57. Zavala F., Tam J. P., Masuda A. Synthetic peptides as antigens for the detection of humoral immunity to Plasmodium falciparum sporozoites. J Immunol Methods. 1986 Oct 23;93(1):55–61. doi: 10.1016/0022-1759(86)90432-1. [DOI] [PubMed] [Google Scholar]

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