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Pathophysiology of severe falciparum malaria in man

Published online by Cambridge University Press:  23 August 2011

D. A. Warrell
Affiliation:
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU

Extract

The term severe falciparum malaria implies an infection with manifestations and complications which are potentially fatal in man, the natural host for this parasite. Much that has been written on the pathophysiology of animal malarias is of doubtful relevance to the understanding of the mechanism of Plasmodium falciparum infection in man. The clinical picture of severe P. falciparum infection differs in several respects from severe animal malarias, even those of non-human primates. Cerebral dysfunction is the most common severe manifestation of falciparum malaria in man. Coma develops suddenly after a generalized convulsion or gradually towards the end of the first week of illness. There are signs of a symmetrical upper motor neurone lesion and brain-stem dysfunction, but only about 5% of survivors show persisting neurological deficit after 2 or 3 days of unconsciousness. The mortality of cerebral malaria depends on how it is defined and on the predominant age group and other factors. In patients with proved acute P. falciparum infection with unrousable coma, in whom other causes of encephalopathy have been excluded, the mortality is between 15 and 50% despite treatment with antimalarial drugs (Warrell, Looareesuwan, Warrell, Kasemsarn, Intaraprasert, Bunnag & Harinasuta, 1982).

Type
Research Article
Copyright
Copyright © Cambridge University Press 1987

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References

REFERENCES

Abdalla, S. H. (1986). Red cell associated IgG in patients suffering from Plasmodium falciparum malaria. British Journal of Haematology 62, 1319.CrossRefGoogle ScholarPubMed
Abdalla, S. & Weatherall, D. J. (1982). The direct antiglobulin test in P. falciparum malaria. British Journal of Haematology 51, 415–25.CrossRefGoogle ScholarPubMed
Adam, C., Geniteau, M., Gougerot-Pocidalo, M., Veeroust, P., Lebras, J., Gilbert, C. & Morel-Maroger, L. (1981). Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria. Infection and Immunity 31, 530–5.CrossRefGoogle ScholarPubMed
Aikawa, M., Uni, Y., Andrutis, A. T. & Howard, R. J. (1986). Membrane-associated electron-dense material of the asexual stages of Plasmodium falciparum: evidence for movement from the intracellular parasite to the erythrocyte membrane. American Journal of Tropical Medicine and Hygiene 35, 3036.CrossRefGoogle Scholar
Aley, S. B., Sherwood, J. A. & Howard, R. J. (1984). Knob-positive and knob-negative Plasmodium falciparum differ in expression of strain-specific malarial antigen on the surface of infected erythrocytes. Journal of Experimental Medicine 160, 1585–90.CrossRefGoogle ScholarPubMed
Barnwell, J. W., Ockenhouse, C. F. & Knowles, D. M. (1985). Monoclonal antibody 0KM5 inhibits the in vitro binding of Plasmodium falciparum-infected erythrocytes to monocytes, endothelial and C32 melanoma cells. Journal of Immunology 135, 3494–7.CrossRefGoogle ScholarPubMed
Berger, M., Birch, L. M. & Conte, N. F. (1967). The nephrotic syndrome secondary to acute glomerulonephritis during falciparum malaria. Annals of Internal Medicine 67, 1163–71.CrossRefGoogle ScholarPubMed
Bhamarapravati, N., Boonpucknavig, S., Boonpucknavig, V. & Yaemboonruang, C. (1973). Glomerular changes in acute Plasmodium falciparum infection. Archives of Pathology 96, 289–93.Google ScholarPubMed
Blackie, W. K. (1944). Blackwater fever. Clinical Proceedings 3, 272312.Google Scholar
Blanloeil, Y., Baron, D., De Lajartre, A. Y. & Nicolas, F. (1980). Acute respiratory distress syndromes (ARDS) in cerebral malaria (author's translation). Semaine des Hopitaux, Paris 56. 1088–90.Google Scholar
Boonpucknavig, V. & Sitprija, V. (1979). Renal disease in acute Plasmodium falciparum infection in man. Kidney International 16, 4452.CrossRefGoogle ScholarPubMed
Bray, R. S. & Sinden, R. E. (1979). The sequestration of Plasmodium falciparum infected erythrocytes in the placenta. Transactions of the Royal Society of Tropical Medicine and Hygiene 73, 716–19.CrossRefGoogle ScholarPubMed
Bygbjerg, I. C. & Lanng, C. (1982). Septicaemia as a complication of falciparum malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 705.CrossRefGoogle ScholarPubMed
Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N. & Williamson, B. (1975). An endo toxin-induced serum factor that causes necrosis of tumors. Proceedings of the National Academy of Sciences, USA 72, 3666–70.CrossRefGoogle Scholar
Chongsuphajaisiddhi, T., Kasemuth, R., Tejavanija, S. & Harinasuta, T. (1971). Changes in blood volume in falciparum malaria. South East Asian Journal of Tropical Medicine and Public Health 2, 344–50.Google ScholarPubMed
Clark, I. A. (1978). Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis. Lancet ii, 75–7.CrossRefGoogle Scholar
Clark, I. A. (1981). Thromboxane may be important in the oxygen damage and hypotension of malaria. Medical Hypotheses 7, 625–31.CrossRefGoogle Scholar
Clark, I. A. (1982). Suggested importance of monokines in pathophysiology of endotoxin shock and malaria. Klinische Wochenschrift 60, 656–8.CrossRefGoogle ScholarPubMed
Clark, I. A. & Hunt, N. H. (1983). Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria. Infection and Immunity 39, 16.CrossRefGoogle ScholarPubMed
Clark, I. A., Hunt, N. H. & Cowden, N. B. (1986a). Immunopathology of malaria. In Immunology, Immunopathology and Immunoprophylaxis of Parasitic Infections, (ed. Soulsby, E. J. L.), CRC Press (in the Press).Google Scholar
Clark, I. A., Hunt, N. H. & Cowden, W. B. (1986b). Oxygen derived free radicals in the pathogenesis of parasitic disease. Advances in Parasitology (In the Press).CrossRefGoogle Scholar
Cohen, S., McGregor, I. A. & Carrington, S. (1961). Gamma-globulin and acquired immunity to human malaria. Nature, London 192, 733–7.CrossRefGoogle ScholarPubMed
Cranston, W. I. (1966). Temperature regulation. British Medical Journal 3, 6975.CrossRefGoogle Scholar
Cranston, H. A., Boylan, C. W. & Carroll, G. L. (1984). Plasmodium falciparum maturation abolishes physiological red cell deformability. Science 223, 400–2.CrossRefGoogle ScholarPubMed
Daniels, C. W. & Newham, H. B. (1923). Laboratory Studies in Tropical Medicine, pp. 130137. London: John Bale Sons & Danielsson Ltd.Google Scholar
David, P. H., Hommel, M., Miller, L. H., Udeinya, I. J. & Oligino, L. D. (1983). Parasite sequestration in Plasmodium falciparum malaria: spleen and antibody modulation of cytoadherence of infected erythrocytes. Proceedings of the National Academy of Sciences, USA 80, 5075–9.CrossRefGoogle ScholarPubMed
De Brito, T., Barone, A. A. & Faria, R. M. (1969). Human liver biopsy in P. falciparum and P. vivax malaria. A light and electron microscopy study. Virchows Archiv Abt. A. Pathologische Anatomie 348, 220–9.Google Scholar
Dennis, L. H., Eicheleberg, J. W., Inman, M. M. & Conrad, M. E. (1967). Depletion of coagulation factors in drug-resistant Plasmodium falciparum malaria. Blood 29, 713–21.Google ScholarPubMed
Desowitz, R. S., Miller, L. H., Buchanan, R. D. & Permpanich, B. (1969). The sites of deep vascular schizogony in Plasmodium coatneyi malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 63, 198202.CrossRefGoogle ScholarPubMed
Devakul, K., Harinasuta, T. & Reid, H. A. (1966). 125I-labelled fibrinogen in cerebral malaria. Lancet ii, 886–8.CrossRefGoogle Scholar
Duarte, M. I. S., Coebett, C. E. P., Boulos, M. & Amato Neto, V. (1985). Ultrastructure of the lung in falciparum malaria. American Journal of Tropical Medicine and Hygiene 34, 31–5.CrossRefGoogle ScholarPubMed
Dudgeon, L. S. (1921). A case of malignant malaria. Transactions of the Ophthalmological Societies of the United Kingdom 41, 236–8.Google Scholar
Dudgeon, L. S. & Clarke, C. (1917). A contribution to the microscopical histology of malaria. Lancet ii, 153–6.CrossRefGoogle Scholar
Dudgeon, L. S. & Clarke, C. (1918). Investigation of fatal cases of pernicious malaria caused by P. falciparum in Macedonia. Quarterly Journal of Medicine 12, 372–90.Google Scholar
Edington, G. M. (1954). Cerebral malaria in the Gold Coast African: four autopsy reports. Annals of Tropical Medicine and Parasitology 48, 300–6.CrossRefGoogle ScholarPubMed
Edington, G. M. & Gilles, H. M. (1969). Pathology in the Tropics, London: Edward Arnold.Google Scholar
Facer, C. A. (1980). Direct Coombs antiglobulin reactions in Gambian children with Plasmodium falciparum malaria. II. Specificity of erythrocyte-bound IgG. Clinical and Experimental Immunology 39, 279–88.Google ScholarPubMed
Feldman, H. A. & Murphy, F. D. (1945). The effect of alterations in blood volume on the anemia and hypoproteinemia of human malaria. Journal of Clinical Investigation 24, 780–92.CrossRefGoogle ScholarPubMed
Fisher, C. S. W. (1983). Clinical curio: acidosis and hypoglycaemia in malaria. British Medical Journal 286, 1261.Google Scholar
Fitz-Hugh, T., Pepper, D. S. & Hopkins, H. U. (1944). The cerebral form of malaria. Bulletin of the US Army Medical Department 83, 3948.Google Scholar
Fletcher, A. & Maegraith, B. (1972). The metabolism of the malaria parasite and its hosts. Advances in Parasitology 10, 3148.CrossRefGoogle Scholar
Flint, J., Hill, A. V. S. & Bowden, D. K. (1986). High frequencies of α-thalassaemia are the result of natural selection by malaria. Nature, London 321, 744–50.CrossRefGoogle ScholarPubMed
Fremount, H. N. & Miller, L. H. (1975). Deep vascular schizogony in Plasmodium fragile: organ distribution and ultrastructure of erythrocytes adherent to vascular endothelium. American Journal of Tropical Medicine and Hygiene 24, 18.CrossRefGoogle ScholarPubMed
Futrakul, P., Boonpucknavig, V., Boonpucknavig, S., Mitrakul, C. & Bhamarapravati, N. (1974). Acute glomerulonephritis complicating Plasmodium falciparum infection. Clinical Pediatrics 13, 281–3.CrossRefGoogle ScholarPubMed
Garnham, P. C. C. (1970). The role of the spleen in protozoal infections with special reference to splenectomy. Acta Tropica 27, 114.Google ScholarPubMed
Gaskell, J. F. & Millar, W. L. (1920). Studies on malignant malaria in Macedonia. Quarterly Journal of Medicine 13, 381426.CrossRefGoogle Scholar
Goodwin, L. G. & Richards, W. H. G. (1960). Pharmacologically active peptides in the blood and urine of animals infected with Babesia rodhaini and other pathogenic organisms. British Journal of Pharmacology and Chemotherapy 15, 152–9.CrossRefGoogle ScholarPubMed
Hall, A. P., Charoendhum, D. & Sonkom, P. (1974-1975). Pulmonary edema due to fluid overload in falciparum malaria. Annual Progress Report of the South East Asian Treaty Organization Medical Research Laboratories, pp. 226233.Google Scholar
Hartenbower, D. L., Kantor, G. L. & Rosen, V. J. (1972). Renal failure due to acute glomerulonephritis during falciparum malaria: case report. Military Medicine 74–6.CrossRefGoogle Scholar
Herzog, C., Ellis, C. J., Innes, J. A. & Fletcher, K. A. (1982). Possible role of drug malabsorption in recrudescence of falciparum malaria. Lancet ii, 1157–8.CrossRefGoogle Scholar
Hoffman, S. L. (1986). Treatment of malaria. Clinics in Tropical Medicine and Communicable Diseases 1, 171224.Google Scholar
Hollenberg, N. K., Epstein, M. & Rosen, S. M. (1968). Acute oliguric renal failure in man: evidence for preferential renal cortical ischemia. Medicine 47, 455–74.CrossRefGoogle ScholarPubMed
Hughes, T. A. (1925). Effects of quinine on the sugar of the blood. Indian Journal of Medical Research 13, 321–36.Google Scholar
James, M. F. M. (1985). Pulmonary damage associated with falciparum malaria: a report often cases. Annals of Tropical Medicine and Parasitology 79, 123–38.CrossRefGoogle ScholarPubMed
Jaroonvesama, N. (1972). Intravascular coagulation in falciparum malaria. Lancet i. 221–3.CrossRefGoogle Scholar
Jervis, H. R., Sprinz, H., Johnson, A. J. & Wellde, B. T. (1972). Experimental infection with Plasmodium falciparum in Aotus monkeys. II. Observations on host pathology. American Journal of Tropical Medicine and Hygiene 21, 272–81.CrossRefGoogle ScholarPubMed
Karney, W. W. & Tong, M. J. (1972). Malabsorption in Plasmodium falciparum malaria. American Journal of Tropical Medicine and Hygiene 21, 15.CrossRefGoogle ScholarPubMed
Klebanoff, S. J., Vadas, M. A., Harlan, J. M., Sparks, L. H., Gamble, J. R., Agosti, J. M. & Waltersdorph, A. M. (1986). Stimulation of neutrophils by tumor necrosis factors. Journal of Immunology 136, 4220–5.CrossRefGoogle Scholar
Knisely, M. H. & Bloch, E. H. (1942). Microscopic observations of intravascular agglutination of red cells and consequent sludging of the blood in human diseases. Anatomical Record 82, 426.Google Scholar
Knisely, M. H., Stratman-Thomas, W. K. & Elliot, T. S. (1941). Observations on circulating blood in the small vessels of internal organs in living Macaca rhesus infected with malarial parasites. Anatomical Record 79, 90.Google Scholar
Knisely, M. H., Stratman-Thomas, W. K., Elliot, T. S. & Bloch, E. H. (1945). Knowlesi malaria in monkeys. I. Microscopic pathological circulatory physiology of rhesus monkeys during acute Plasmodium knowlesi malaria in monkeys (a motion picture). Journal of the National Malaria Society 4, 285300.Google Scholar
Knisely, M. H., Stratman-Thomas, W. K., Elliot, T. S. & Bloch, E. H. (1964). Knowlesi malaria in monkeys. II. A first step in the separation of the mechanical pathological circulatory factors of one sludge disease from possible specific toxic factors of that disease. Angiology 15, 411–16.CrossRefGoogle Scholar
Knüttgen, H. J. (1963). Das menschliche Knochenmark bei akuten Malaria Infektionen. Zeitschrift für Tropenmedizin und Parasitologie 14, 423–66.Google Scholar
Lancet (1966). Adult respiratory distress syndrome. Lancet i, 301–3.Google Scholar
Laveran, C. L. A. (1893). Paludism. Translated by Martin, J. W., London, New Sydenham Society.CrossRefGoogle Scholar
Laveran, A. (1907). Traité du Paludisme, 2nd edn. p. 486. Paris: Masson et Cie.Google Scholar
Lawler, J. (1986). The structural and functional properties of thrombospondin. Blood 67, 11971209.CrossRefGoogle ScholarPubMed
Lee, M. V., Ambrus, J. L., De Souza, J. M. & Lee, R. V. (1982). Diminished red blood cell deformability in uncomplicated human malaria. A preliminary report. Journal of Cellular Physiology 114, 245–51.Google Scholar
Leech, J. H., Aley, S. B., Miller, L. H. & Howard, R. J. (1984a). Plasmodium falciparum malaria: cytoadherence of infected erythrocytes to endothelial cells and associated changes in the erythrocyte membrane. Progress in Clinical Biological Research 155, 6377.Google ScholarPubMed
Leech, J. H., Barnwell, J. W., Miller, L. H. & Howard, R. J. (1984b). Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-iniected erythrocytes. Journal of Experimental Medicine 159, 1567–75.CrossRefGoogle ScholarPubMed
Lessire, H., Coyette, Y., Lambert, M., Mailleux, J. P., Coche, E. & Reynaert, M. (1984). Complications pulmonaires de la malaria a propos de deux cas. Acta Clinica Belgica 39, 290–5.CrossRefGoogle Scholar
Looareesuwan, S., Phillips, R. E., White, N. J., Kietinun, S., Karbwang, J., Rackow, C., Turner, R. C. & Warrell, D. A. (1985). Quinine and severe falciparum malaria in late pregnancy. Lancet ii, 48.CrossRefGoogle Scholar
Looareesuwan, S., Warrell, D. A., White, N. J., Suntharasamai, P., Chanthavanich, P., Sundaravej, K., Juel-Jensen, B. E., Bunnag, D. & Harinasuta, T. (1983). Do patients with cerebral malaria have cerebral oedema? A computed tomography study. Lancet i, 434–7.CrossRefGoogle Scholar
Luse, S. A. & Miller, L. H. (1971). P. falciparum malaria ultrastructure of parasitized erythrocytes in cardiac vessels. American Journal of Tropical Medicine and Hygiene 20, 655–60.CrossRefGoogle Scholar
Macpherson, G. G., Warrell, M. J., White, N. J., Looareesuwan, S. & Warrell, D. A. (1985). Human cerebral malaria: a quantitative ultrastructural analysis of parasitized erythrocyte sequestration. American Journal of Pathology 119, 385401.Google ScholarPubMed
Maegraith, B. G. (1948). Pathological Processes in Malaria and Blackwater Fever. Oxford: Blackwell Scientific.Google Scholar
Maegraith, B. G. (1952). Recent advances in tropical medicine: blackwater fever. West African Medical Journal 1. 410.Google Scholar
Maegraith, B. & Fletcher, A. (1972). The pathogenesis of mammalian malaria. Advances in Parasitology 10, 4975.CrossRefGoogle ScholarPubMed
Mahakur, A. C.Danda, S. N., Nanda, B. K., Bose, T. K., Satapathy, S. R. & Misra, Y. (1983). Malarial acute renal failure. Journal of the Association of Physicians of India 31, 633–6.Google ScholarPubMed
Malloy, J. P., Brooks, M. H., Barry, K. G., Wilt, S. & McNeil, J. S. (1967). Pathophysiology of acute falciparum malaria. II. Fluid compartmentalization. American Journal of Medicine 43, 745–50.CrossRefGoogle ScholarPubMed
Marchiafava, E. & Bignami, A. (1894). On Summer-Autumn Malarial Fevers. Translated from the 1st Italian edition by Thompson, J. H., pp. 112117. London, New Sydenham Society.Google Scholar
Marsh, K. & Greenwood, B. M. (1986). The immunopathology of malaria. Clinics in Tropical Medicine and Communicable Diseases 1, 91125.Google Scholar
Martell, R. W., Kallenbach, J. & Zwi, S. (1979). Pulmonary oedema in falciparum malaria. British Medical Journal 1, 1763–4.CrossRefGoogle ScholarPubMed
Martin, C., Auffray, J. P., Saux, P., Chevalier, A., Aubert, C. & Gouin, F. (1982). Oedème pulmonaire au cours d' un accès pernicieux palustre. Evolution favourable sous ventilation artificielle avec pression positive de fin d'expiration. La Nouvelle Presse Medicate 11, 1638.Google Scholar
Merry, A. H., Looareesuwan, S., Phillips, R. E., Chanthavanich, P., Supanaranond, W., Warrell, D. A. & Weatherall, D. J. (1986). Evidence against immune haemolysis in falciparum malaria in Thailand. British Journal of Haematology 64, 187–94.CrossRefGoogle ScholarPubMed
Migasena, S. (1983). Hypoglycaemia in falciparum malaria. Annals of Tropical Medicine and Parasitology 77, 323–4.CrossRefGoogle ScholarPubMed
Miller, L. H. (1969). Distribution of mature trophozoites and schizonts of Plasmodium falciparum in the organs of Aotus trivergatus, the night monkey. American Journal of Tropical Medicine and Hygiene 18, 860–5.CrossRefGoogle Scholar
Miller, L. H., Chien, S. & Usami, S. (1972). Decreased deformability of Plasmodium coatneyi infected red cells and its possible relation to cerebral malaria. American Journal of Tropical Medicine and Hygiene 21, 133–7.CrossRefGoogle ScholarPubMed
Miller, L. H., Fremount, H. N. & Luse, S. A. (1971). Deep vascular schizogony of Plasmodium knowlesi in Macaco, mulatta. Distribution in organs and ultrastructure of parasitized red cells. American Journal of Tropical Medicine and Hygiene 20, 816–24.CrossRefGoogle Scholar
Miller, L. H., Usami, S. & Chien, S. (1971). Alteration in the rheological properties of Plasmodium knowlesi-infected red cells. A possible mechanism for capillary obstruction. Journal of Clinical Investigation 50, 1451–5.CrossRefGoogle ScholarPubMed
Msengi, A. E. & Yohani, A. (1984). Malaria control in Tanzania. Lancet ii, 1159–60.CrossRefGoogle Scholar
Narula, A. S., Gopinathan, V. P. & Narula, H. S. (1985). Hypoglycaemia in falciparum malaria – an unusual manifestation. Journal of the Association of Physicians of India 33, 740–1.Google ScholarPubMed
Nawroth, P. P., Bank, I., Handley, D., Cassimeris, J., Chess, L. & Stern, D. (1986). Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. Journal of Experimental Medicine 163, 1363–75.CrossRefGoogle ScholarPubMed
Ojo-Amaize, E. A., Salimono, L. S.Williams, A. I., Akinwolere, O. A., Shabo, R., Alm, G. V. & Wigzell, H. (1984). Positive correlation between degree of parasitaemia, interferon titers and natural killer cell activity in Plasmodium falciparum-infected children. Journal of Immunology 127, 2296–300.CrossRefGoogle Scholar
Olsson, R. A. & Johnston, E. H. (1969). Histopathology changes and small-bowel absorption in falciparum malaria. American Journal of Tropical Medicine and Hygiene 18, 355–9.CrossRefGoogle ScholarPubMed
Onabanjo, A. O. (1974). Pathophysiological role of plasma kinins in malaria. West African Journal Pharm Drug Res 1, 2431.Google ScholarPubMed
Onabanjo, A. O., Bhabani, A. R. & Maegraith, B. G. (1970). The significance of kinin-destroying enzymes activity in Plasmodium knowlesi malarial infection. British Journal of Experimental Pathology 51. 534–40.Google ScholarPubMed
Onabanjo, A. O. & Maegraith, B. G. (1970). Kallikrein as a pathogenic agent in Plasmodium knowlesi infection in Macaca mulatta. British Journal of Experimental Pathology 51, 523–33.Google ScholarPubMed
Overman, R. R., Hill, T. S. & Wong, Y. T. (1949). Physiological studies in the human malarial host. I. Blood, plasma, ‘extra cellular’ fluid volumes, and ionic balance in therapeutic P. vivax and P. falciparum infections. Journal of the National Malaria Society 8, 14.Google Scholar
Panich, V. (1981). Glucose-6-phosphate dehydrogenase deficiency Part 2. Tropical Asia. Clinical Haematology 10, 800–14.CrossRefGoogle ScholarPubMed
Parbtani, A. & Cameron, J. S. (1979). Experimental nephritis associated with plasmodium infection in mice. Kidney International 16, 5363.CrossRefGoogle ScholarPubMed
Petchclai, B., Chutanondh, R., Hiranras, S. & Benjapongs, W. (1977). Activation of classical and alternate complement pathways in acute falciparum malaria. Journal of the Medical Association of Thailand 60, 174–6.Google ScholarPubMed
Phillips, R. E., Looareesuwan, S., Warrell, D. A., Lee, S. H., Karbwang, J., Warrell, M. J., White, N. J., Swasdichai, C. & Weatherall, D. J. (1986a). The importance of anaemia in cerebral and uncomplicated falciparum malaria: role of complications, dyserythropoiesis and iron sequestration. Quarterly Journal of Medicine 58, 305–23.Google ScholarPubMed
Phillips, R. E., Looareesuwan, S., White, N. J., Chanthavanich, P., Karbwang, J., Supanaranond, W., Turner, R. C. & Warrell, D. A. (1986b). Hypoglycaemia and antimalarial drugs: quinidine and release of insulin. British Medical Journal 292, 1319–21.CrossRefGoogle ScholarPubMed
Phillips, R. E., Warrell, D. A., Looareesuwan, S., Turner, R. C.Bloom, S. R., Quantrill, D. & Moore, R. A. (1986c). Effectiveness of SMS201-995, a synthetic, long-acting somatostatin analogue, in treatment of quinine-induced hyperinsulinaemia. Lancet i, 713-16.CrossRefGoogle Scholar
Phillips, R. E., White, N. J., Looareesuwan, S., Chanthavanich, P., Karbwang, J. & Warrell, D. A. (1984). Acute renal failure in falciparum malaria in eastern Thailand: successful use of peritoneal dialysis. Eleventh International Congress for Tropical Medicine and Malaria, Calgary, Canada.Google Scholar
Punyagupta, S., Srichaikul, T., Nitiyanant, P. & Petchclai, B. (1974). Acute pulmonary insufficiency in falciparum malaria: summary of 12 cases with evidence of disseminated intravascular coagulation. American Journal of Tropical Medicine and Hygiene 23, 551–9.CrossRefGoogle ScholarPubMed
Raventos-Suarez, C., Kaul, D. K., Macaluso, F. & Nagel, R. L. (1985). Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes. Proceedings of the National Academy of Science, USA 82, 3829–33.CrossRefGoogle ScholarPubMed
Reid, H. A. & Nkrumah, F. K. (1972). Fibrin-degradation products in cerebral malaria. Lancet i, 218–21.CrossRefGoogle Scholar
Rest, J. R. (1983). Pathogenesis of cerebral malaria in golden hamsters and inbred mice. Contributions to Microbiology and Immunology 7, 139–46.Google ScholarPubMed
Rest, J. R. & Wright, D. H. (1979). Electron microscopy of cerebral malaria in golden hamsters (Mesocricetus auratus) infected with Plasmodium berghei. Journal of Pathology 127, 115–20.CrossRefGoogle ScholarPubMed
Rigdon, R. H. & Stratman-Thomas, W. K. (1942). A study of the pathological lesions in P. knowlesi infection in M. rhesus monkeys. American Journal of Tropical Medicine 22, 329–39.Google Scholar
Roberts, D. D. D., Sherwood, J. A., Spitalnik, S. L., Panton, L. J., Howard, R. J., Dixit, V. M., Frazier, W. A., Miller, L. H. & Ginsburg, V. (1985). Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature, London 318, 64-6.CrossRefGoogle ScholarPubMed
Ross, G. R. (1962). Blackwater fever in Southern Rhodesia in retrospect. Central African Journal of Medicine 8, 294–7.Google ScholarPubMed
Sassa, S., Kawakami, M. & Cerami, A. (1983). Inhibition of the growth and differentiation of erythroid precursor cells by an endotoxin-induced mediator from peritoneal macrophages. Proceedings of the National Academy of Sciences, USA 80, 1717–20.CrossRefGoogle ScholarPubMed
Schmahl, F. W., Schlote, W., Urbascher, B., Betz, E., Heuser, D. & Heckers, H. (1982). Reactions of endothelial cells of cerebral vessels in endotoxic shock. Proceedings of the 5th Annual Conference on Shock, pp. 192–3.Google Scholar
Schmid, A. H. (1974). Cerebral malaria. On the nature and significance of vascular changes. Europ. Neurol. 12, 197208.CrossRefGoogle ScholarPubMed
Schmidt, J. A., Udeinya, I. J., Leech, J. H., Hay, R. J., Aikawa, M., Barnwell, J., Green, I. & Miller, L. H. (1982). An amelonotic melanoma cell line bears receptors for the knob ligand on infected erythrocytes. Journal of Clinical Investigation 70, 379–86.CrossRefGoogle Scholar
Schmidt, L. H. (1978). Plasmodium falciparum and Plasmodium vivax infections in the owl monkey (Aotus trivirgatus). I. The courses of untreated infections. American Journal of Tropical Medicine and Hygiene 27, 671732.CrossRefGoogle ScholarPubMed
Schnitzer, B., Sodeman, T. M., Mead, M. L. & Contacos, P. G. (1973). An ultrastructural study of the red pulp of the spleen in malaria. Blood 41, 207–17.CrossRefGoogle ScholarPubMed
Segal, H. E., Hall, A. P., Jewel, J. S., Pearlman, E. N., Na-Nakorn, A. & Mettaprakong, V. (1974). Gastrointestinal function, quinine absorption and parasitic response in falciparum malaria. South East Asian Journal of Tropical Medicine and Public Health 5, 499503.Google ScholarPubMed
Singh, B., Ho, M., Warrell, D. A., Looareesuwan, S. & Hommel, M. (1986). Plasmodium falciparum: inhibition/reversal of cytoadherence of Thai isolates with local immune sera. Annual Meeting of the American Society of Tropical Medicine and Hygiene, Denver, Colorado, 7-11 December, 1986. Abstract 76 (in the Press).Google Scholar
Sitprija, V., Vongsthongsri, M., Poshyachinda, V. & Arthachinta, S. (1977). Renal failure in malaria: a pathophysiologic study. Nephron 18, 277–87.CrossRefGoogle ScholarPubMed
Skirrow, M. B., Chongsuphajaisiddhi, T. & Maegraith, B. G. (1964). The circulation in malaria II Portal angiography in monkeys (Macaca mulatta) infected with Plasmodium knowlesi and in shock following manipulation of the gut. Annals of Tropical Medicine and Parasitology 58, 502–10.CrossRefGoogle ScholarPubMed
Smith, D. H. & Theakston, R. D. G. (1970). Comments on the ultrastructure of human erythocytes infected with Plasmodium malariae. Annals of Tropical Medicine and Parasitology 64, 329.CrossRefGoogle Scholar
Spitz, S. (1946). The pathology of acute falciparum malaria. Military Surgery 99, 555–72.CrossRefGoogle ScholarPubMed
Srichaikul, T., Puwasatien, P., Puwasatien, P., Karnjanajetanee, J. & Bokisch, V. A. (1975). Complement changes and disseminated intravascular coagulation in Plasmodium falciparum malaria. Lancet i, 770–2.CrossRefGoogle Scholar
Stone, W. J., Hanchett, J. F. & Knepshield, J. H. (1972). Acute renal insufficiency due to falciparum malaria. Review of 42 cases. Archives of Internal Medicine 129, 620–8.CrossRefGoogle ScholarPubMed
Tella, A. & Maegraith, B. G. (1966). Studies on bradykinin and bradykininogen in malaria. Annals of Tropical Medicine and Parasitology 60, 304–17.CrossRefGoogle ScholarPubMed
Tharavanij, S., Warrell, M. J., Tantivanich, S., Tapcharisri, P., Chongsa-Nguan, M., Prasertsiriroj, V. & Patarapotikul, J. (1984). Factors contributing to the development of cerebral malaria. 1. Humoral immune responses. American Journal of Tropical Medicine and Hygiene 33, 111.CrossRefGoogle Scholar
Theakston, R. D. G., Fletcher, K. A., Maskrey, P. & Maegraith, B. G. (1971). Ultrastructural studies of the effects of malarial toxic factors on normal mouse tissues. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 3.Google ScholarPubMed
Toro, G. & Roman, G. (1978). Cerebral malaria. A disseminated vasculomyelinopathy. Archives of Neurology 35, 271–5.CrossRefGoogle ScholarPubMed
Trager, W., Rudzinska, M. A. & Bradbury, P. C. (1966). The fine structure of P. falciparum and its host erythroctyes in natural malarial infections in man. Bulletin of the World Health Organization 35, 883–5.Google Scholar
Tubbs, H. (1980). Endotoxin in human and murine malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 74, 121–3.CrossRefGoogle ScholarPubMed
Udeinya, I. J., Graves, P. M., Carter, R. & Aikawa, M. (1983a). Plasmodium falciparum: effect of time in continuous culture on binding to human endothelial cells and amelanotic melanoma cells. Experimental Parasitology 56, 207–14.CrossRefGoogle ScholarPubMed
Udeinya, I. J., Miller, L. H., McGregor, J. A., Jensen, J. B. (1983b). Plasmodium falciparum strain-specific antibody blocks binding of infected erythrocytes to amelanotic melanoma cells. Nature, London 303, 429–31.CrossRefGoogle ScholarPubMed
Udeinya, I. J., Schmidt, J. A., Aikawa, M., Miller, L. H. & Green, I. (1981). Falciparum malaria – infected erythrocytes specifically bind to cultured human endothelial cells. Science 213, 555–7.CrossRefGoogle ScholarPubMed
Usawattanakul, W., Tharavanij, S., Warrell, D. A., Looareesuwan, S., White, N. J., Supavej, J. & Soikratoke, S. (1985). Factors contributing to the development of cerebral malaria. II. Endotoxin. Clinical and Experimental Immunology 61, 562–8.Google Scholar
Walter, P. R., Garin, Y. & Blot, P. (1982). Placental pathologic changes in malaria. A histologic and ultrastructural study. American Journal of Pathology 109, 330–42.Google ScholarPubMed
Warrell, D. A. (1983). The impact of clinical investigation on two third world diseases: cerebral malaria and louse-borne relapsing fever. Advanced Medicine 19 (ed. Saunders, K. B.), pp. 99111. Pitman.Google Scholar
Warrell, D. A., Looareesuwan, S., Phillips, R. E., White, N. J., Warrell, M. J., Chapel, H. M., Areekul, S. & Tharavanij, S. (1986). Function of the blood–cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis. American Journal of Tropical Medicine and Hygiene 35, 882–9.CrossRefGoogle ScholarPubMed
Warrell, D. A., Looareesuwan, S., Warrell, M. J., Kasemsarn, P., Intaraprasert, R., Bunnag, D. & Harinasuta, T. (1982). Dexamethasone proves deleterious in cerebral malaria. A double-line trial in 100 comatose patients. New England Journal of Medicine 306, 313–19.CrossRefGoogle Scholar
White, N. J. (1986). Malaria pathophysiology. Clinics in Tropical Medicine and Communicable Diseases 1, 5590.Google Scholar
White, N. J., Warrell, D. A., Chanthavanich, P., Looareesuwan, S., Warrell, M. J., Krishna, S., Williamson, D. H. & Turner, R. C. (1983). Severe hypoglycemia and hyperinsulinemia in falciparum malaria. New England Journal of Medicine 309, 61–6.CrossRefGoogle ScholarPubMed
White, N. J., Warrell, D. A. & Looareesuwan, S. (1984). Cerebral blood flow and metabolism in cerebral malaria. Eleventh International Congress for Tropical Medicine and Malaria, Calgary, Canada. p. 116 (Abstract).Google Scholar
White, N. J., Warrell, D. A., Looareesuwan, S., Chanthavanich, P., Phillips, R. E. & Pongpaew, P. (1985). Pathophysiological and prognostic significance of cerebrospinal fluid lactate in cerebral malaria. Lancet i, 776–8.CrossRefGoogle Scholar
Wickramasuriya, G. A. W. (1937). Malaria and Ankylostomiasis in the Pregnant Woman. Their more Serious Complications and Sequelae. London: Oxford University Press.Google Scholar
World Health Organization (1986). Severe and complicated malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, Suppl. 150.Google Scholar
Wright, D. H. (1968). The effect of neonatal thymectomy on the survival of golden hamsters and rats infected with Plasmodium berghei. British Journal of Experimental Pathology 49, 379–84.Google Scholar
Yelich, M. R. & Filkins, J. P. (1980). Mechanism of hyperinsulinemia in endotoxicosis. American Journal of Physiology 239, E15661.Google ScholarPubMed
Yoeli, M. (1976). Cerebral malaria – the quest for suitable experimental models in parasite diseases of man. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 2435.CrossRefGoogle ScholarPubMed
Yoeli, M. & Hargreaves, B. J. (1974). Brain capillary blockage produced by a virulent strain of rodent malaria. Science 184, 572–3.CrossRefGoogle ScholarPubMed
Yu, W. A., Yu, M. C. & Young, P. A. (1974). Ultrastructural changes in the cerebrovascular endothelium induced by a diet high in linoleic acid and deficient in vitamin E. Experimental and Molecular Pathology 21, 289–99.CrossRefGoogle ScholarPubMed