Abstract
Hyperimmune globulin can inhibit and reverse the cytoadherence between Plasmodium falciparum-infected erythrocytes and melanoma cells in vitro. Cytoadherence is believed to mediate disease in cerebral malaria. Therefore we studied the efficacy of i.v. immunoglobulin, purified from the plasma of local semi-immune blood donors, as an adjunct to standard treatment for cerebral malaria in Malawian children. The immunoglobulin preparation (IFAT antimalarial antibody titre 1:5120) recognized erythrocyte-associated antigens of each of 22 Malawian P. falciparum isolates studied, and reversed binding of Malawian isolates to melanoma cells. Immunoglobulin did not reverse binding to human monocytes or to cells of the human histiocytic lymphoma cell line U937. Thirty-one children with P. falciparum parasitaemia and unrousable coma were enrolled. All were treated with i.v. quinine dihydrochloride; in addition patients were randomized to receive either immunoglobulin (400 mg/kg by i.v. infusion over 3 h) or placebo (albumen and sucrose by similar infusion) in a double blind trial with sequential analysis. Of 16 patients receiving immunoglobulin, five (31%) died and five survivors had neurological sequelae. Of 15 patients receiving placebo, one (7%) died and two had sequelae. Parasite clearance, fever clearance and coma resolution times in survivors were similar in the two groups. Although the difference in outcome between the two groups was not significant, the trial was stopped because immunoglobulin was demonstrated not to be superior to placebo.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- COHEN S., McGREGOR I. A., CARRINGTON S. Gamma-globulin and acquired immunity to human malaria. Nature. 1961 Nov 25;192:733–737. doi: 10.1038/192733a0. [DOI] [PubMed] [Google Scholar]
- David P. H., Hommel M., Miller L. H., Udeinya I. J., Oligino L. D. Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5075–5079. doi: 10.1073/pnas.80.16.5075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diggs C., Joseph K., Flemmings B., Snodgrass R., Hines F. Protein synthesis in vitro by cryopreserved Plasmodium falciparum. Am J Trop Med Hyg. 1975 Sep;24(5):760–763. doi: 10.4269/ajtmh.1975.24.760. [DOI] [PubMed] [Google Scholar]
- Goldring J. D., Molyneux M. E., Taylor T., Wirima J., Hommel M. Plasmodium falciparum: diversity of isolates from Malawi in their cytoadherence to melanoma cells and monocytes in vitro. Br J Haematol. 1992 Jul;81(3):413–418. doi: 10.1111/j.1365-2141.1992.tb08249.x. [DOI] [PubMed] [Google Scholar]
- Greenwood B. M., Brueton M. J. Complement activation in children with acute malaria. Clin Exp Immunol. 1974 Oct;18(2):267–272. [PMC free article] [PubMed] [Google Scholar]
- Hommel M., Hughes M., Bond P., Crampton J. M. Antibodies and DNA probes used to analyze variant populations of the Indochina-1 strain of Plasmodium falciparum. Infect Immun. 1991 Nov;59(11):3975–3981. doi: 10.1128/iai.59.11.3975-3981.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hénin Y., Maréchal V., Barré-Sinoussi F., Chermann J. C., Morgenthaler J. J. Inactivation and partition of human immunodeficiency virus during Kistler and Nitschmann fractionation of human blood plasma. Vox Sang. 1988;54(2):78–83. doi: 10.1111/j.1423-0410.1988.tb01621.x. [DOI] [PubMed] [Google Scholar]
- Kempf C., Jentsch P., Poirier B., Barré-Sinoussi F., Morgenthaler J. J., Morell A., Germann D. Virus inactivation during production of intravenous immunoglobulin. Transfusion. 1991 Jun;31(5):423–427. doi: 10.1046/j.1537-2995.1991.31591263197.x. [DOI] [PubMed] [Google Scholar]
- MacPherson G. G., Warrell M. J., White N. J., Looareesuwan S., Warrell D. A. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985 Jun;119(3):385–401. [PMC free article] [PubMed] [Google Scholar]
- Molyneux M. E., Taylor T. E., Wirima J. J., Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med. 1989 May;71(265):441–459. [PubMed] [Google Scholar]
- Molyneux M. E., Taylor T. E., Wirima J. J., Grau G. E. Tumour necrosis factor, interleukin-6, and malaria. Lancet. 1991 May 4;337(8749):1098–1098. doi: 10.1016/0140-6736(91)91745-g. [DOI] [PubMed] [Google Scholar]
- Sabchareon A., Burnouf T., Ouattara D., Attanath P., Bouharoun-Tayoun H., Chantavanich P., Foucault C., Chongsuphajaisiddhi T., Druilhe P. Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg. 1991 Sep;45(3):297–308. doi: 10.4269/ajtmh.1991.45.297. [DOI] [PubMed] [Google Scholar]
- Shore A., Leary P., Teitel J. M. Comparison of accessory cell functions of endothelial cells and monocytes: IL-2 production by T cells and PFC generation. Cell Immunol. 1986 Jun;100(1):210–223. doi: 10.1016/0008-8749(86)90020-1. [DOI] [PubMed] [Google Scholar]
- Singh B., Ho M., Looareesuwan S., Mathai E., Warrell D. A., Hommel M. Plasmodium falciparum: inhibition/reversal of cytoadherence of Thai isolates to melanoma cells by local immune sera. Clin Exp Immunol. 1988 Apr;72(1):145–150. [PMC free article] [PubMed] [Google Scholar]
- Taylor T. E., Molyneux M. E., Wirima J. J., Fletcher K. A., Morris K. Blood glucose levels in Malawian children before and during the administration of intravenous quinine for severe falciparum malaria. N Engl J Med. 1988 Oct 20;319(16):1040–1047. doi: 10.1056/NEJM198810203191602. [DOI] [PubMed] [Google Scholar]
- Tharavanij S., Tapchaisri P., Mahakunkijcharoen Y., Looareesuwan S. Antibody against a ring-infected erythrocyte surface antigen in cerebral and non-cerebral malaria patients. Trans R Soc Trop Med Hyg. 1988;82(3):385–388. doi: 10.1016/0035-9203(88)90128-9. [DOI] [PubMed] [Google Scholar]
- 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]
- Udomsangpetch R., Aikawa M., Berzins K., Wahlgren M., Perlmann P. Cytoadherence of knobless Plasmodium falciparum-infected erythrocytes and its inhibition by a human monoclonal antibody. Nature. 1989 Apr 27;338(6218):763–765. doi: 10.1038/338763a0. [DOI] [PubMed] [Google Scholar]
- White N. J., Krishna S. Treatment of malaria: some considerations and limitations of the current methods of assessment. Trans R Soc Trop Med Hyg. 1989 Nov-Dec;83(6):767–777. doi: 10.1016/0035-9203(89)90322-2. [DOI] [PubMed] [Google Scholar]
- White N. J., Miller K. D., Marsh K., Berry C. D., Turner R. C., Williamson D. H., Brown J. Hypoglycaemia in African children with severe malaria. Lancet. 1987 Mar 28;1(8535):708–711. doi: 10.1016/s0140-6736(87)90354-0. [DOI] [PubMed] [Google Scholar]