1921
Volume 68, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Several studies have focused their attention on the relationship between host genetic factors and susceptibility/resistance to severe malaria. However, there is a paucity of information concerning the role of host genetic factors in asymptomatic malaria, a form of low-grade infection without clinical symptoms. We investigated in this study the potential relationship between the host (human) genetic polymorphisms (glucose-6-phosphate dehydrogenase [G6PD], mannose binding lectin [MBL], tumor necrosis factor α [TNF α] and , and nitric oxide synthase 2 [NOS2]) and the prevalence and profile of asymptomatic infection in 158 Gabonese schoolchildren. We found that G6PD A heterozygous females (18 of 74) have a low prevalence of asymptomatic malaria (38.9% versus 67.3%; = 0.03, by chi-square test). Children heterozygous for TNFα (25 of 156) carry high number of diverse infecting parasite genotypes (2.5 versus 1.99; variance F = 3.05). No statistically significant association was found between MBL, TNF α , or NOS2 polymorphisms and asymptomatic malaria. Upon combining our data on asymptomatic forms with those from the literature for others forms, we conclude that G6PD A heterozygous females are protected against all forms of malaria, and that the TNF α allele confers protection against clinical malaria.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2003.68.186
2003-02-01
2017-11-24
Loading full text...

Full text loading...

/deliver/fulltext/14761645/68/2/0680186.html?itemId=/content/journals/10.4269/ajtmh.2003.68.186&mimeType=html&fmt=ahah

References

  1. Greenwood BM, 1987. Asymptomatic malaria infections: do they matter? Parasitol Today 3 : 206–214.
  2. Staalsoe T, Hviid L, 1998. The role of variant-specific immunity in asymptomatic malaria infections: maintaining a fine balance.Parasitol Today 14 : 177–178.
  3. Kurtzhals JAL, Addae MM, Akanmori BD, Dunyo S, Koram KA, Appawu MA, Nkrumah FK, Hviid L, 1999. Anaemia caused by asymptomatic Plasmodium falciparum infection in semi-immune African schoolchildren. Trans R Soc Trop Med Hyg 93 : 623–627.
  4. Gendrel D, Kombila M, Nardou M, Gendrel C, Djouba F, Martz M, Richard-Lenoble D, 1992. Malaria and haemoglobin S : interactions in African children. Presse Med 21 : 887–890.
  5. Nagel RL, Roth EF, 1989. Malaria and red cell defects. Blood 74 : 1213–1221.
  6. Williams TN, Maitland K, Bennett S, Ganczakowski M, Peto TE, Newbold CI, Bowden DK, Weatherall DJ, Clegg JB, 1996.High incidence of malaria in alpha-thalassaemic children. Nature 383 : 522–525.
  7. Hirono A, Beutler E, 1988. Molecular cloning and nucleotide sequence of cDNA for human glucose-6-phosphate dehydrogenase variant A(–). Proc Natl Acad Sci USA 85 : 3951–3954.
  8. Roth EF, Raventos-Suarez C, Rinaldi A, Nagel RL, 1983. Glucose-6-phosphate dehydrogenase deficiency inhibits in vitro growth of Plasmodium falciparum. Proc Natl Acad Sci USA 80 : 298–299.
  9. Usanga EA, Luzzatto L, 1985. Adaptation of Plasmodium falciparum to glucose 6-phosphate dehydrogenase-deficient host red cells by production of parasite-encoded enzyme. Nature 313 : 793–795.
  10. Luty AJF, Kun JFJ, Kremsner PG, 1998. Mannose-binding lectin plasma levels and gene polymorphisms in Plasmodium falciparum malaria. J Infect Dis 178 : 1221–1224.
  11. McGuire W, Hill AVS, Allsopp CEM, Greenwood BM, Kwiatkowski D, 1994. Variation in the TNF-α promoter region associated with susceptibility to cerebral malaria. Nature 371 : 508–511.
  12. McGuire W, Knight JC, Hill AVS, Allsopp CEM, Greenwood BM, Kwiatkowski D, 1999. Severe malarial anaemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. J Infect Dis 179 : 287–290.
  13. Knight JC, Udalova I, Hill AVS, Greenwood BM, Peshu N, Marsh K, Kwiatkowski D, 1999. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. Nat Genet 22 : 145–150.
  14. Burgner D, Xu W, Rockett K, Gravenor M, Charles IG, Hill AVS, Kwiatkowski D, 1998. Inducible nitric oxide synthase polymorphism and fatal cerebral malaria. Lancet 352 : 1193–1194.
  15. Kun JFJ, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG, 1998. Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 351 : 265–266.
  16. Turner MW, 1996. Mannose binding lectin: the pluripotent molecule of the innate immune system. Immunol Today 11 : 532–540.
  17. Super M, Thiel S, Lu J, Levinsky RJ, Turner MW, 1989. Association of low levels of mannan-binding protein with a common defect of opsonisation. Lancet i : 1236–1239.
  18. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW, 1997. Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation. Proc Natl Acad Sci USA 94 : 3195–3199.
  19. Wattavidanage J, Carter R, Perera KLRL, Munasingha A, Bandara S, McGuiness D, Wickramasinghe AR, Alles HK, Mendis KN, Premawansa S, 1999. TNFα 2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans. Clin Exp Immunol 115 : 350–355.
  20. Burgner D, Rockett K, Kwiatkowski D, 1999. Nitric oxide and infectious diseases. Arch Dis Child 81 : 185–188.
  21. Elissa N, Karch S, Bureau P, Ollomo B, Lawoko M, Yangari P,Ebang B, Georges AJ, 1999. Malaria transmission in a region of savannah-forest mosaic, Haut-ogooué, Gabon. J Am Mosq Control Assoc 15 : 15–23.
  22. Ntoumi F, Mercereau-Puijalon O, Ossari S, Luty A, Reltien J, Georges A, Millet P, 1997. Plasmodium falciparum : Sickle-cell trait is associated with higher prevalence of multiple infections in Gabonese children with asymptomatic infections. Exp Parasitol 87 : 39–46.
  23. Ntoumi F, Contamin H, Rogier C, Bonnefoy S, Trape JF, Mercereau-Puijalon O, 1995. Age dependent carriage of multiple Plasmodium falciparum merozoite surface antigen-2 alleles in asymptomatic malaria infections. Am J Trop Med Hyg 52 : 81–88.
  24. Lell B, May J, Schmidt-Ott RJ, Lehman LG, Luckner D, Greve B, Matousek P, Schmid D, Herbich K, Mockenhaupt FP, Meyer CG, Kremsner PG, 1999. The role of red blood cell polymorphisms in resistance and susceptibility to malaria. Clin Infect Dis 28 : 794–799.
  25. Bienzle U, Ayeni O, Lucas AO, Luzzatto L, 1972. Glucose-6-phosphate dehydrogenase and malaria. Greater resistance of female heterozygous for enzyme deficiency and males with non-deficient variant. Lancet 1 : 107–110.
  26. Ruwende C, Khoo SC, Snow RW, Yates SNR, Kwiatkowski D, Gupta S, Warn P, Allsopp CEM, Gilbert SC, Peschu N, Newbold CI, Greenwood BM, Marsh K, Hill AVS, 1995. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria. Nature 376 : 246–249.
  27. Luzzato L, Sodeinde O, Martini G, 1983. Genetic variation in the host and adaptive phenomena in Plasmodium falciparum infection, in malaria and the red cell. Ciba Found Symp 94 : 159–173.
  28. Janney SK, Joist JJ, Fitch CD, 1986. Excess release of ferriheme in G6PD-deficient erythrocytes: possible cause of haemolysis and resistance to malaria. Blood 67 : 331–333.
  29. Bellamy R, Ruwende C, McAdam KPWJ, Thursz M, Sumiya M, Summerfield J, Gilbert SC, Corrah T, Kwiatkowski D, Whittle HC, Hill AVS, 1998. Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans. Q J Med 91 : 13–18.
  30. Zimmerman PA, Guderian RH, Nutman TB, 1996. A new TNFA promoter allele identified in South American Blacks. Immunogenetics 44 : 485–486.
  31. Koss K, Satsangi J, Fanning GC, Welsh KI, Jewell DP, 2000. Cytokine (TNFα, LTα and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun 1 : 185–190.
  32. Engelbrecht F, Felger I, Genton B, Alpers M, Beck HP, 1995.Plasmodium falciparum: malaria morbidity is associated with specific merozoite surface antigen 2 genotypes. Exp Parasitol 81 : 90–96.
  33. Barragan A, Kremsner PG, Wahlgren M, Carlson J, 2000. Blood group A antigen is a coreceptor in Plasmodium falciparum rosetting. Infect Immun 68 : 2971–2975.
  34. Lipscombe RJ, Sumiya M, Hill AV, Lau YL, Levinsky RJ, Summerfield JA, Turner MW, 1992. High frequencies in African and non-African populations of independent mutations in the mannose binding protein gene. Hum Mol Genet 1 : 709–715.
  35. Wilson AG, di Giovine FS, Blakemore AI, Duff GW, 1992. Single base polymorphism in the human tumor necrosis factor alpha (TNF alpha) gene detectable by Nco I restriction of PCR product. Hum Mol Genet 1 : 353.
  36. D’Alfonso S, Richiardi PM, 1994. A polymorphic variation in a putative regulation box of the TNFA promoter region. Immnogenetics 39 : 150–154.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2003.68.186
Loading
/content/journals/10.4269/ajtmh.2003.68.186
Loading

Data & Media loading...

  • Received : 07 Mar 2002
  • Accepted : 28 May 2002

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error