Skip to main content
PMC home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1997 Sep 29;352(1359):1385–1394. doi: 10.1098/rstb.1997.0124

Host-parasite interaction and morbidity in malaria endemic areas.

K Marsh 1, R W Snow 1
PMCID: PMC1692020  PMID: 9355131

Abstract

Severe morbidity due to Plasmodium falciparum is a major health problem in African children. The patterns of morbidity in endemic areas are modified by the immune response, and vary markedly with transmission intensity. Severe disease falls into three overlapping syndromes: coma, respiratory distress, and severe anaemia. Recently, it has become clear that metabolic acidosis plays a major role in the pathogenesis of severe disease and is particularly important in the overlap between the different clinical syndromes. We propose that the different manifestations of severe malarial morbidity arise from the interaction of a limited number of pathogenic processes: red cell destruction, toxin-mediated activation of cytokine cascades, and infected cell sequestration in tissue microvascular beds. The pattern of severe morbidity varies with age within any one endemic area, with severe anaemia predominating in the youngest children and coma having its highest incidence in older children. Between endemic areas there is a marked variation in mean age of children with severe malaria, and therefore in the importance of different clinical syndromes. The shift in mean age is due to a combination of increased challenge and more rapid development of immunity at higher levels of transmission. Recent comparative studies indicate that at higher levels of transmission the net effect of these shifts may be a paradoxical reduction in total severe malarial morbidity.

Full Text

The Full Text of this article is available as a PDF (194.2 KB).

Selected References

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

  1. Abdalla S., Weatherall D. J., Wickramasinghe S. N., Hughes M. The anaemia of P. falciparum malaria. Br J Haematol. 1980 Oct;46(2):171–183. doi: 10.1111/j.1365-2141.1980.tb05956.x. [DOI] [PubMed] [Google Scholar]
  2. Al Yaman F. M., Mokela D., Genton B., Rockett K. A., Alpers M. P., Clark I. A. Association between serum levels of reactive nitrogen intermediates and coma in children with cerebral malaria in Papua New Guinea. Trans R Soc Trop Med Hyg. 1996 May-Jun;90(3):270–273. doi: 10.1016/s0035-9203(96)90243-6. [DOI] [PubMed] [Google Scholar]
  3. Allan R. J., Beattie P., Bate C., Van Hensbroek M. B., Morris-Jones S., Greenwood B. M., Kwiatkowski D. Strain variation in tumor necrosis factor induction by parasites from children with acute falciparum malaria. Infect Immun. 1995 Apr;63(4):1173–1175. doi: 10.1128/iai.63.4.1173-1175.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allan R. J., Rowe A., Kwiatkowski D. Plasmodium falciparum varies in its ability to induce tumor necrosis factor. Infect Immun. 1993 Nov;61(11):4772–4776. doi: 10.1128/iai.61.11.4772-4776.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Anstey N. M., Weinberg J. B., Hassanali M. Y., Mwaikambo E. D., Manyenga D., Misukonis M. A., Arnelle D. R., Hollis D., McDonald M. I., Granger D. L. Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression. J Exp Med. 1996 Aug 1;184(2):557–567. doi: 10.1084/jem.184.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnwell J. W., Asch A. S., Nachman R. L., Yamaya M., Aikawa M., Ingravallo P. A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J Clin Invest. 1989 Sep;84(3):765–772. doi: 10.1172/JCI114234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baruch D. I., Pasloske B. L., Singh H. B., Bi X., Ma X. C., Feldman M., Taraschi T. F., Howard R. J. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell. 1995 Jul 14;82(1):77–87. doi: 10.1016/0092-8674(95)90054-3. [DOI] [PubMed] [Google Scholar]
  8. Bate C. A., Kwiatkowski D. A monoclonal antibody that recognizes phosphatidylinositol inhibits induction of tumor necrosis factor alpha by different strains of Plasmodium falciparum. Infect Immun. 1994 Dec;62(12):5261–5266. doi: 10.1128/iai.62.12.5261-5266.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Berendt A. R., Simmons D. L., Tansey J., Newbold C. I., Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature. 1989 Sep 7;341(6237):57–59. doi: 10.1038/341057a0. [DOI] [PubMed] [Google Scholar]
  10. Brewster D. R., Kwiatkowski D., White N. J. Neurological sequelae of cerebral malaria in children. Lancet. 1990 Oct 27;336(8722):1039–1043. doi: 10.1016/0140-6736(90)92498-7. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Clark I. A., Chaudhri G., Cowden W. B. Roles of tumour necrosis factor in the illness and pathology of malaria. Trans R Soc Trop Med Hyg. 1989 Jul-Aug;83(4):436–440. doi: 10.1016/0035-9203(89)90240-x. [DOI] [PubMed] [Google Scholar]
  13. Clark I. A., Chaudhri G. Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. Br J Haematol. 1988 Sep;70(1):99–103. doi: 10.1111/j.1365-2141.1988.tb02440.x. [DOI] [PubMed] [Google Scholar]
  14. Clark I. A., Cowden W. B., Butcher G. A. TNF and inhibition of growth of Plasmodium falciparum. Immunol Lett. 1990 Aug;25(1-3):175–178. doi: 10.1016/0165-2478(90)90111-3. [DOI] [PubMed] [Google Scholar]
  15. Clark I. A., MacMicking J. D., Gray K. M., Rockett K. A., Cowden W. B. Malaria mimicry with tumor necrosis factor. Contrasts between species of murine malaria and Plasmodium falciparum. Am J Pathol. 1992 Feb;140(2):325–336. [PMC free article] [PubMed] [Google Scholar]
  16. Clark I. A., Rockett K. A. Nitric oxide and parasitic disease. Adv Parasitol. 1996;37:1–56. doi: 10.1016/s0065-308x(08)60218-3. [DOI] [PubMed] [Google Scholar]
  17. Crawley J., Smith S., Kirkham F., Muthinji P., Waruiru C., Marsh K. Seizures and status epilepticus in childhood cerebral malaria. QJM. 1996 Aug;89(8):591–597. doi: 10.1093/qjmed/89.8.591. [DOI] [PubMed] [Google Scholar]
  18. Dye C., Hasibeder G. Population dynamics of mosquito-borne disease: effects of flies which bite some people more frequently than others. Trans R Soc Trop Med Hyg. 1986;80(1):69–77. doi: 10.1016/0035-9203(86)90199-9. [DOI] [PubMed] [Google Scholar]
  19. English M. C., Waruiru C., Lightowler C., Murphy S. A., Kirigha G., Marsh K. Hyponatraemia and dehydration in severe malaria. Arch Dis Child. 1996 Mar;74(3):201–205. doi: 10.1136/adc.74.3.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. English M., Marsh V., Amukoye E., Lowe B., Murphy S., Marsh K. Chronic salicylate poisoning and severe malaria. Lancet. 1996 Jun 22;347(9017):1736–1737. doi: 10.1016/s0140-6736(96)90809-0. [DOI] [PubMed] [Google Scholar]
  21. English M., Murphy S., Mwangi I., Crawley J., Peshu N., Marsh K. Interobserver variation in respiratory signs of severe malaria. Arch Dis Child. 1995 Apr;72(4):334–336. doi: 10.1136/adc.72.4.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. English M., Waruiru C., Amukoye E., Murphy S., Crawley J., Mwangi I., Peshu N., Marsh K. Deep breathing in children with severe malaria: indicator of metabolic acidosis and poor outcome. Am J Trop Med Hyg. 1996 Nov;55(5):521–524. doi: 10.4269/ajtmh.1996.55.521. [DOI] [PubMed] [Google Scholar]
  23. English M., Waruiru C., Marsh K. Transfusion for respiratory distress in life-threatening childhood malaria. Am J Trop Med Hyg. 1996 Nov;55(5):525–530. doi: 10.4269/ajtmh.1996.55.525. [DOI] [PubMed] [Google Scholar]
  24. Erunkulu O. A., Hill A. V., Kwiatkowski D. P., Todd J. E., Iqbal J., Berzins K., Riley E. M., Greenwood B. M. Severe malaria in Gambian children is not due to lack of previous exposure to malaria. Clin Exp Immunol. 1992 Aug;89(2):296–300. doi: 10.1111/j.1365-2249.1992.tb06948.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Fried M., Duffy P. E. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science. 1996 Jun 7;272(5267):1502–1504. doi: 10.1126/science.272.5267.1502. [DOI] [PubMed] [Google Scholar]
  26. Gardner J. P., Pinches R. A., Roberts D. J., Newbold C. I. Variant antigens and endothelial receptor adhesion in Plasmodium falciparum. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3503–3508. doi: 10.1073/pnas.93.8.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Grau G. E., Kindler V., Piguet P. F., Lambert P. H., Vassalli P. Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation. J Exp Med. 1988 Oct 1;168(4):1499–1504. doi: 10.1084/jem.168.4.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Grau G. E., Piguet P. F., Vassalli P., Lambert P. H. Tumor-necrosis factor and other cytokines in cerebral malaria: experimental and clinical data. Immunol Rev. 1989 Dec;112:49–70. doi: 10.1111/j.1600-065x.1989.tb00552.x. [DOI] [PubMed] [Google Scholar]
  29. Grau G. E., Taylor T. E., Molyneux M. E., Wirima J. J., Vassalli P., Hommel M., Lambert P. H. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med. 1989 Jun 15;320(24):1586–1591. doi: 10.1056/NEJM198906153202404. [DOI] [PubMed] [Google Scholar]
  30. Greenwood B., Marsh K., Snow R. Why do some African children develop severe malaria? Parasitol Today. 1991 Oct;7(10):277–281. doi: 10.1016/0169-4758(91)90096-7. [DOI] [PubMed] [Google Scholar]
  31. Gupta S., Hill A. V., Kwiatkowski D., Greenwood A. M., Greenwood B. M., Day K. P. Parasite virulence and disease patterns in Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3715–3719. doi: 10.1073/pnas.91.9.3715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Gupta S., Maiden M. C., Feavers I. M., Nee S., May R. M., Anderson R. M. The maintenance of strain structure in populations of recombining infectious agents. Nat Med. 1996 Apr;2(4):437–442. doi: 10.1038/nm0496-437. [DOI] [PubMed] [Google Scholar]
  33. Jensen M. D., Conley M., Helstowski L. D. Culture of Plasmodium falciparum: the role of pH, glucose, and lactate. J Parasitol. 1983 Dec;69(6):1060–1067. [PubMed] [Google Scholar]
  34. Kern P., Hemmer C. J., Van Damme J., Gruss H. J., Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med. 1989 Aug;87(2):139–143. doi: 10.1016/s0002-9343(89)80688-6. [DOI] [PubMed] [Google Scholar]
  35. Koram K. A., Bennett S., Adiamah J. H., Greenwood B. M. Socio-economic determinants are not major risk factors for severe malaria in Gambian children. Trans R Soc Trop Med Hyg. 1995 Mar-Apr;89(2):151–154. doi: 10.1016/0035-9203(95)90472-7. [DOI] [PubMed] [Google Scholar]
  36. Krishna S., Waller D. W., ter Kuile F., Kwiatkowski D., Crawley J., Craddock C. F., Nosten F., Chapman D., Brewster D., Holloway P. A. Lactic acidosis and hypoglycaemia in children with severe malaria: pathophysiological and prognostic significance. Trans R Soc Trop Med Hyg. 1994 Jan-Feb;88(1):67–73. doi: 10.1016/0035-9203(94)90504-5. [DOI] [PubMed] [Google Scholar]
  37. Kwiatkowski D., Hill A. V., Sambou I., Twumasi P., Castracane J., Manogue K. R., Cerami A., Brewster D. R., Greenwood B. M. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet. 1990 Nov 17;336(8725):1201–1204. doi: 10.1016/0140-6736(90)92827-5. [DOI] [PubMed] [Google Scholar]
  38. Kwiatkowski D. Malarial toxins and the regulation of parasite density. Parasitol Today. 1995 Jun;11(6):206–212. doi: 10.1016/0169-4758(95)80079-4. [DOI] [PubMed] [Google Scholar]
  39. Lackritz E. M., Campbell C. C., Ruebush T. K., 2nd, Hightower A. W., Wakube W., Steketee R. W., Were J. B. Effect of blood transfusion on survival among children in a Kenyan hospital. Lancet. 1992 Aug 29;340(8818):524–528. doi: 10.1016/0140-6736(92)91719-o. [DOI] [PubMed] [Google Scholar]
  40. Looareesuwan S., Ho M., Wattanagoon Y., White N. J., Warrell D. A., Bunnag D., Harinasuta T., Wyler D. J. Dynamic alteration in splenic function during acute falciparum malaria. N Engl J Med. 1987 Sep 10;317(11):675–679. doi: 10.1056/NEJM198709103171105. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Magowan C., Wollish W., Anderson L., Leech J. Cytoadherence by Plasmodium falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins on infected erythrocytes. J Exp Med. 1988 Oct 1;168(4):1307–1320. doi: 10.1084/jem.168.4.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Marsh K., English M., Crawley J., Peshu N. The pathogenesis of severe malaria in African children. Ann Trop Med Parasitol. 1996 Aug;90(4):395–402. doi: 10.1080/00034983.1996.11813068. [DOI] [PubMed] [Google Scholar]
  44. Marsh K., Forster D., Waruiru C., Mwangi I., Winstanley M., Marsh V., Newton C., Winstanley P., Warn P., Peshu N. Indicators of life-threatening malaria in African children. N Engl J Med. 1995 May 25;332(21):1399–1404. doi: 10.1056/NEJM199505253322102. [DOI] [PubMed] [Google Scholar]
  45. Marsh K., Howard R. J. Antigens induced on erythrocytes by P. falciparum: expression of diverse and conserved determinants. Science. 1986 Jan 10;231(4734):150–153. doi: 10.1126/science.2417315. [DOI] [PubMed] [Google Scholar]
  46. Marsh K. Malaria--a neglected disease? Parasitology. 1992;104 (Suppl):S53–S69. doi: 10.1017/s0031182000075247. [DOI] [PubMed] [Google Scholar]
  47. Marsh K., Marsh V. M., Brown J., Whittle H. C., Greenwood B. M. Plasmodium falciparum: the behavior of clinical isolates in an in vitro model of infected red blood cell sequestration. Exp Parasitol. 1988 Apr;65(2):202–208. doi: 10.1016/0014-4894(88)90123-3. [DOI] [PubMed] [Google Scholar]
  48. Mbogo C. N., Snow R. W., Khamala C. P., Kabiru E. W., Ouma J. H., Githure J. I., Marsh K., Beier J. C. Relationships between Plasmodium falciparum transmission by vector populations and the incidence of severe disease at nine sites on the Kenyan coast. Am J Trop Med Hyg. 1995 Mar;52(3):201–206. doi: 10.4269/ajtmh.1995.52.201. [DOI] [PubMed] [Google Scholar]
  49. McGuire W., Hill A. V., Allsopp C. E., Greenwood B. M., Kwiatkowski D. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature. 1994 Oct 6;371(6497):508–510. doi: 10.1038/371508a0. [DOI] [PubMed] [Google Scholar]
  50. Molineaux L. Plasmodium falciparum malaria: some epidemiological implications of parasite and host diversity. Ann Trop Med Parasitol. 1996 Aug;90(4):379–393. doi: 10.1080/00034983.1996.11813067. [DOI] [PubMed] [Google Scholar]
  51. Molyneux M. E., Looareesuwan S., Menzies I. S., Grainger S. L., Phillips R. E., Wattanagoon Y., Thompson R. P., Warrell D. A. Reduced hepatic blood flow and intestinal malabsorption in severe falciparum malaria. Am J Trop Med Hyg. 1989 May;40(5):470–476. doi: 10.4269/ajtmh.1989.40.470. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Nussler A. K., Eling W., Kremsher P. G. Patients with Plasmodium falciparum malaria and Plasmodium vivax malaria show increased nitrite and nitrate plasma levels. J Infect Dis. 1994 Jun;169(6):1418–1419. doi: 10.1093/infdis/169.6.1418. [DOI] [PubMed] [Google Scholar]
  54. Ockenhouse C. F., Klotz F. W., Tandon N. N., Jamieson G. A. Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3175–3179. doi: 10.1073/pnas.88.8.3175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Ockenhouse C. F., Tegoshi T., Maeno Y., Benjamin C., Ho M., Kan K. E., Thway Y., Win K., Aikawa M., Lobb R. R. Human vascular endothelial cell adhesion receptors for Plasmodium falciparum-infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1. J Exp Med. 1992 Oct 1;176(4):1183–1189. doi: 10.1084/jem.176.4.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Oo M. M., Aikawa M., Than T., Aye T. M., Myint P. T., Igarashi I., Schoene W. C. Human cerebral malaria: a pathological study. J Neuropathol Exp Neurol. 1987 Mar;46(2):223–231. doi: 10.1097/00005072-198703000-00009. [DOI] [PubMed] [Google Scholar]
  57. Phillips R. E., Pasvol G. Anaemia of Plasmodium falciparum malaria. Baillieres Clin Haematol. 1992 Apr;5(2):315–330. doi: 10.1016/s0950-3536(11)80022-3. [DOI] [PubMed] [Google Scholar]
  58. Pober J. S. Warner-Lambert/Parke-Davis award lecture. Cytokine-mediated activation of vascular endothelium. Physiology and pathology. Am J Pathol. 1988 Dec;133(3):426–433. [PMC free article] [PubMed] [Google Scholar]
  59. Ringwald P., Peyron F., Lepers J. P., Rabarison P., Rakotomalala C., Razanamparany M., Rabodonirina M., Roux J., Le Bras J. Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines. Infect Immun. 1993 Dec;61(12):5198–5204. doi: 10.1128/iai.61.12.5198-5204.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Roberts 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. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature. 1985 Nov 7;318(6041):64–66. doi: 10.1038/318064a0. [DOI] [PubMed] [Google Scholar]
  61. Rowe A., Obeiro J., Newbold C. I., Marsh K. Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun. 1995 Jun;63(6):2323–2326. doi: 10.1128/iai.63.6.2323-2326.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schofield L., Novakovic S., Gerold P., Schwarz R. T., McConville M. J., Tachado S. D. Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. J Immunol. 1996 Mar 1;156(5):1886–1896. [PubMed] [Google Scholar]
  63. Sherman I. W., Crandall I., Smith H. Membrane proteins involved in the adherence of Plasmodium falciparum-infected erythrocytes to the endothelium. Biol Cell. 1992;74(2):161–178. doi: 10.1016/0248-4900(92)90022-s. [DOI] [PubMed] [Google Scholar]
  64. Sherry B. A., Alava G., Tracey K. J., Martiney J., Cerami A., Slater A. F. Malaria-specific metabolite hemozoin mediates the release of several potent endogenous pyrogens (TNF, MIP-1 alpha, and MIP-1 beta) in vitro, and altered thermoregulation in vivo. J Inflamm. 1995;45(2):85–96. [PubMed] [Google Scholar]
  65. Snow R. W., Armstrong J. R., Forster D., Winstanley M. T., Marsh V. M., Newton C. R., Waruiru C., Mwangi I., Winstanley P. A., Marsh K. Childhood deaths in Africa: uses and limitations of verbal autopsies. Lancet. 1992 Aug 8;340(8815):351–355. doi: 10.1016/0140-6736(92)91414-4. [DOI] [PubMed] [Google Scholar]
  66. Snow R. W., Omumbo J. A., Lowe B., Molyneux C. S., Obiero J. O., Palmer A., Weber M. W., Pinder M., Nahlen B., Obonyo C. Relation between severe malaria morbidity in children and level of Plasmodium falciparum transmission in Africa. Lancet. 1997 Jun 7;349(9066):1650–1654. doi: 10.1016/S0140-6736(97)02038-2. [DOI] [PubMed] [Google Scholar]
  67. Taylor T. E., Borgstein A., Molyneux M. E. Acid-base status in paediatric Plasmodium falciparum malaria. Q J Med. 1993 Feb;86(2):99–109. [PubMed] [Google Scholar]
  68. Todd J. E., De Francisco A., O'Dempsey T. J., Greenwood B. M. The limitations of verbal autopsy in a malaria-endemic region. Ann Trop Paediatr. 1994;14(1):31–36. doi: 10.1080/02724936.1994.11747689. [DOI] [PubMed] [Google Scholar]
  69. Turner G. D., Morrison H., Jones M., Davis T. M., Looareesuwan S., Buley I. D., Gatter K. C., Newbold C. I., Pukritayakamee S., Nagachinta B. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994 Nov;145(5):1057–1069. [PMC free article] [PubMed] [Google Scholar]
  70. Udeinya I. J., Akogyeram C. O. Induction of adhesiveness in human endothelial cells by Plasmodium falciparum-infected erythrocytes. Am J Trop Med Hyg. 1993 Apr;48(4):488–495. doi: 10.4269/ajtmh.1993.48.488. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES