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Protection against malaria in the hemoglobinopathies

David J Roberts, MA, MB, D Phil
Section Editors
Stanley L Schrier, MD
Johanna Daily, MD, MSc
Deputy Editors
Jennifer S Tirnauer, MD
Elinor L Baron, MD, DTMH


The history of genetics and the study of malaria are inextricably linked. The burden of disease due to malaria across much of the world has selected for a series of very visible traits of major medical importance, including the alleles of genes encoding hemoglobin, red cell enzymes, and membrane proteins. Furthermore, as might be expected from the intricate life cycle of the parasite in the human host, it now appears that many other genes may also influence the outcome of infection, including some that modulate the immune responses and others that encode for endothelial proteins.

The genetic resistance to malarial infection, particularly falciparum malaria, associated with the hemoglobinopathies, will be reviewed here. Resistance associated with abnormalities in red cell surface antigens or cytoskeleton is discussed separately. (See "Protection against malaria by abnormalities in red cell surface antigens and cytoskeletal proteins".)


Plasmodium falciparum malaria, the deadly form of malaria, has a life cycle that includes alternating hosts: a sexual cycle in the insect vector (a female) Anopheles mosquito and a human cycle that includes a liver stage and an erythrocytic stage. Genetic resistance to the blood stage has been extensively documented, but the association of HLA class I allotypes with protection from malaria suggests genetic traits resistance also during the hepatic stage of infection [1,2].

Genetic resistance to P. falciparum malaria at the erythrocytic stage may involve one or more of the following mechanisms:

Inhibition of merozoite entry into the red cell [3]

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Literature review current through: Nov 2017. | This topic last updated: Oct 20, 2016.
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  1. Hill AV, Allsopp CE, Kwiatkowski D, et al. Common west African HLA antigens are associated with protection from severe malaria. Nature 1991; 352:595.
  2. Hill AV, Elvin J, Willis AC, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature 1992; 360:434.
  3. Tiffert T, Lew VL, Ginsburg H, et al. The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum. Blood 2005; 105:4853.
  4. Bunyaratvej A, Butthep P, Yuthavong Y, et al. Increased phagocytosis of Plasmodium falciparum-infected erythrocytes with haemoglobin E by peripheral blood monocytes. Acta Haematol 1986; 76:155.
  5. Yuthavong Y, Butthep P, Bunyaratvej A, et al. Impaired parasite growth and increased susceptibility to phagocytosis of Plasmodium falciparum infected alpha-thalassemia or hemoglobin Constant Spring red blood cells. Am J Clin Pathol 1988; 89:521.
  6. Ayi K, Turrini F, Piga A, Arese P. Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood 2004; 104:3364.
  7. Shear HL, Roth EF Jr, Fabry ME, et al. Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria. Blood 1993; 81:222.
  8. Flint J, Harding RM, Clegg JB, Boyce AJ. Why are some genetic diseases common? Distinguishing selection from other processes by molecular analysis of globin gene variants. Hum Genet 1993; 91:91.
  9. May J, Evans JA, Timmann C, et al. Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA 2007; 297:2220.
  10. Aidoo M, Terlouw DJ, Kolczak MS, et al. Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet 2002; 359:1311.
  11. Wiesenfeld SL. Sickle-cell trait in human biological and cultural evolution. Development of agriculture causing increased malaria is bound to gene-pool changes causing malaria reduction. Science 1967; 157:1134.
  12. Mackinnon MJ, Gunawardena DM, Rajakaruna J, et al. Quantifying genetic and nongenetic contributions to malarial infection in a Sri Lankan population. Proc Natl Acad Sci U S A 2000; 97:12661.
  13. Mackinnon MJ, Mwangi TW, Snow RW, et al. Heritability of malaria in Africa. PLoS Med 2005; 2:e340.
  14. Taylor SM, Parobek CM, Fairhurst RM. Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect Dis 2012; 12:457.
  15. BEET EA. Sickle cell disease in the Balovale District of Northern Rhodesia. East Afr Med J 1946; 23:75.
  17. Haldane JB. Disease and Evolution. La Ricerce Scientifica 1949; 19:68.
  18. Gouagna LC, Bancone G, Yao F, et al. Genetic variation in human HBB is associated with Plasmodium falciparum transmission. Nat Genet 2010; 42:328.
  19. ALLISON AC. Protection afforded by sickle-cell trait against subtertian malareal infection. Br Med J 1954; 1:290.
  20. Willcox M, Björkman A, Brohult J. Falciparum malaria and beta-thalassaemia trait in northern Liberia. Ann Trop Med Parasitol 1983; 77:335.
  21. Fleming AF, Storey J, Molineaux L, et al. Abnormal haemoglobins in the Sudan savanna of Nigeria. I. Prevalence of haemoglobins and relationships between sickle cell trait, malaria and survival. Ann Trop Med Parasitol 1979; 73:161.
  22. Marsh K, Otoo L, Hayes RJ, et al. Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans R Soc Trop Med Hyg 1989; 83:293.
  23. Jakobsen PH, Riley EM, Allen SJ, et al. Differential antibody response of Gambian donors to soluble Plasmodium falciparum antigens. Trans R Soc Trop Med Hyg 1991; 85:26.
  24. Scott JA, Berkley JA, Mwangi I, et al. Relation between falciparum malaria and bacteraemia in Kenyan children: a population-based, case-control study and a longitudinal study. Lancet 2011; 378:1316.
  25. Williams TN, Mwangi TW, Wambua S, et al. Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait. Nat Genet 2005; 37:1253.
  26. do Sambo MR, Penha-Gonçalves C, Trovoada MJ, et al. Quantitative trait locus analysis of parasite density reveals that HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia. Malar J 2015; 14:393.
  27. Patel JC, Mwapasa V, Kalilani L, et al. Absence of Association Between Sickle Trait Hemoglobin and Placental Malaria Outcomes. Am J Trop Med Hyg 2016; 94:1002.
  28. Gong L, Maiteki-Sebuguzi C, Rosenthal PJ, et al. Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait. Blood 2012; 119:3808.
  29. Bunn HF. The triumph of good over evil: protection by the sickle gene against malaria. Blood 2013; 121:20.
  30. Roth EF Jr, Friedman M, Ueda Y, et al. Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria. Science 1978; 202:650.
  31. Luzzatto L, Nwachuku-Jarrett ES, Reddy S. Increased sickling of parasitised erythrocytes as mechanism of resistance against malaria in the sickle-cell trait. Lancet 1970; 1:319.
  32. Friedman MJ. Erythrocytic mechanism of sickle cell resistance to malaria. Proc Natl Acad Sci U S A 1978; 75:1994.
  33. Pasvol G, Weatherall DJ, Wilson RJ. Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria. Nature 1978; 274:701.
  34. Pasvol G. The interaction between sickle haemoglobin and the malarial parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg 1980; 74:701.
  35. Olson JA, Nagel RL. Synchronized cultures of P falciparum in abnormal red cells: the mechanism of the inhibition of growth in HbCC cells. Blood 1986; 67:997.
  36. LaMonte G, Philip N, Reardon J, et al. Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance. Cell Host Microbe 2012; 12:187.
  37. Friedman MJ. Ultrastructural damage to the malaria parasite in the sickled cell. J Protozool 1979; 26:195.
  38. Friedman MJ, Roth EF, Nagel RL, Trager W. Plasmodium falciparum: physiological interactions with the human sickle cell. Exp Parasitol 1979; 47:73.
  39. Olivieri O, Vitoux D, Galacteros F, et al. Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes. Blood 1992; 79:793.
  40. Lew VL, Ortiz OE, Bookchin RM. Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability. J Clin Invest 1997; 99:2727.
  41. Schwartz RS, Musto S, Fabry ME, Nagel RL. Two distinct pathways mediate the formation of intermediate density cells and hyperdense cells from normal density sickle red blood cells. Blood 1998; 92:4844.
  42. Ginsburg H, Handeli S, Friedman S, et al. Effects of red blood cell potassium and hypertonicity on the growth of Plasmodium falciparum in culture. Z Parasitenkd 1986; 72:185.
  43. Tanabe K, Izumo A, Kageyama K. Growth of Plasmodium falciparum in sodium-enriched human erythrocytes. Am J Trop Med Hyg 1986; 35:476.
  44. Cappadoro M, Giribaldi G, O'Brien E, et al. Early phagocytosis of glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes parasitized by Plasmodium falciparum may explain malaria protection in G6PD deficiency. Blood 1998; 92:2527.
  45. Diakité SA, Ndour PA, Brousse V, et al. Stage-dependent fate of Plasmodium falciparum-infected red blood cells in the spleen and sickle-cell trait-related protection against malaria. Malar J 2016; 15:482.
  46. Cyrklaff M, Sanchez CP, Kilian N, et al. Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science 2011; 334:1283.
  47. Kilian N, Dittmer M, Cyrklaff M, et al. Haemoglobin S and C affect the motion of Maurer's clefts in Plasmodium falciparum-infected erythrocytes. Cell Microbiol 2013; 15:1111.
  48. Cholera R, Brittain NJ, Gillrie MR, et al. Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A 2008; 105:991.
  49. Opi DH, Ochola LB, Tendwa M, et al. Mechanistic Studies of the Negative Epistatic Malaria-protective Interaction Between Sickle Cell Trait and α(+)thalassemia. EBioMedicine 2014; 1:29.
  50. Guggenmoos-Holzmann I, Bienzle U, Luzzatto L. Plasmodium falciparum malaria and human red cells. II. Red cell genetic traits and resistance against malaria. Int J Epidemiol 1981; 10:16.
  51. Bayoumi RA. The sickle-cell trait modifies the intensity and specificity of the immune response against P. falciparum malaria and leads to acquired protective immunity. Med Hypotheses 1987; 22:287.
  52. Bayoumi RA. Does the mechanism of protection from falciparum malaria by red cell genetic disorders involve a switch to a balanced TH1/TH2 cytokine production mode? Med Hypotheses 1997; 48:11.
  53. EDOZIEN JC, BOYO AE, MORLEY DC. The relationship of serum gamma-globulin concentration to malaria and sickling. J Clin Pathol 1960; 13:118.
  54. Cornille-Brøgger R, Fleming AF, Kagan I, et al. Abnormal haemoglobins in the Sudan savanna of Nigeria. II. Immunological response to malaria in normals and subjects with sickle cell trait. Ann Trop Med Parasitol 1979; 73:173.
  55. Abu-Zeid YA, Abdulhadi NH, Theander TG, et al. Seasonal changes in cell mediated immune responses to soluble Plasmodium falciparum antigens in children with haemoglobin AA and haemoglobin AS. Trans R Soc Trop Med Hyg 1992; 86:20.
  56. Tan X, Traore B, Kayentao K, et al. Hemoglobin S and C heterozygosity enhances neither the magnitude nor breadth of antibody responses to a diverse array of Plasmodium falciparum antigens. J Infect Dis 2011; 204:1750.
  57. Williams TN, Mwangi TW, Roberts DJ, et al. An immune basis for malaria protection by the sickle cell trait. PLoS Med 2005; 2:e128.
  58. Allen SJ, Rowe P, Allsopp CE, et al. A prospective study of the influence of alpha thalassaemia on morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in Gambian children. Trans R Soc Trop Med Hyg 1993; 87:282.
  59. Schwarzer E, Turrini F, Ulliers D, et al. Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment. J Exp Med 1992; 176:1033.
  60. Urban BC, Ferguson DJ, Pain A, et al. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 1999; 400:73.
  61. McGilvray ID, Serghides L, Kapus A, et al. Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood 2000; 96:3231.
  62. Fabry ME, Nagel RL, Pachnis A, et al. High expression of human beta S- and alpha-globins in transgenic mice: hemoglobin composition and hematological consequences. Proc Natl Acad Sci U S A 1992; 89:12150.
  63. Fabry ME, Costantini F, Pachnis A, et al. High expression of human beta S- and alpha-globins in transgenic mice: erythrocyte abnormalities, organ damage, and the effect of hypoxia. Proc Natl Acad Sci U S A 1992; 89:12155.
  64. Nagel RL. A knockout of a transgenic mouse--animal models of sickle cell anemia. N Engl J Med 1998; 339:194.
  65. Hood AT, Fabry ME, Costantini F, et al. Protection from lethal malaria in transgenic mice expressing sickle hemoglobin. Blood 1996; 87:1600.
  66. Ferreira A, Marguti I, Bechmann I, et al. Sickle hemoglobin confers tolerance to Plasmodium infection. Cell 2011; 145:398.
  67. Serjeant GR. Mortality from sickle cell disease in Africa. BMJ 2005; 330:432.
  68. Diallo D, Tchernia G. Sickle cell disease in Africa. Curr Opin Hematol 2002; 9:111.
  69. McAuley CF, Webb C, Makani J, et al. High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya. Blood 2010; 116:1663.
  70. Makani J, Komba AN, Cox SE, et al. Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood 2010; 115:215.
  71. Diop S, Soudré F, Seck M, et al. Sickle-cell disease and malaria: evaluation of seasonal intermittent preventive treatment with sulfadoxine-pyrimethamine in Senegalese patients-a randomized placebo-controlled trial. Ann Hematol 2011; 90:23.
  72. Modiano D, Luoni G, Sirima BS, et al. Haemoglobin C protects against clinical Plasmodium falciparum malaria. Nature 2001; 414:305.
  73. Mockenhaupt FP, Ehrhardt S, Cramer JP, et al. Hemoglobin C and resistance to severe malaria in Ghanaian children. J Infect Dis 2004; 190:1006.
  74. Lopera-Mesa TM, Doumbia S, Konaté D, et al. Effect of red blood cell variants on childhood malaria in Mali: a prospective cohort study. Lancet Haematol 2015; 2:e140.
  75. Travassos MA, Coulibaly D, Laurens MB, et al. Hemoglobin C Trait Provides Protection From Clinical Falciparum Malaria in Malian Children. J Infect Dis 2015; 212:1778.
  76. Kreuels B, Kreuzberg C, Kobbe R, et al. Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth. Blood 2010; 115:4551.
  77. Fairhurst RM, Baruch DI, Brittain NJ, et al. Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria. Nature 2005; 435:1117.
  78. Kilian N, Srismith S, Dittmer M, et al. Hemoglobin S and C affect protein export in Plasmodium falciparum-infected erythrocytes. Biol Open 2015; 4:400.
  79. Friedman MJ, Roth EF, Nagel RL, Trager W. The role of hemoglobins C, S, and Nbalt in the inhibition of malaria parasite development in vitro. Am J Trop Med Hyg 1979; 28:777.
  80. Lin MJ, Nagel RL, Hirsch RE. Acceleration of hemoglobin C crystallization by hemoglobin S. Blood 1989; 74:1823.
  81. Leikin SL, Gallagher D, Kinney TR, et al. Mortality in children and adolescents with sickle cell disease. Cooperative Study of Sickle Cell Disease. Pediatrics 1989; 84:500.
  82. Flatz G. Hemoglobin E: distribution and population dynamics. Humangenetik 1967; 3:189.
  83. Sicard D, Lieurzou Y, Lapoumeroulie C, Labie D. High genetic polymorphism of hemoglobin disorders in Laos. Complex phenotypes due to associated thalassemic syndromes. Hum Genet 1979; 50:327.
  84. Vernes AJ, Haynes JD, Tang DB, et al. Decreased growth of Plasmodium falciparum in red cells containing haemoglobin E, a role for oxidative stress, and a sero-epidemiological correlation. Trans R Soc Trop Med Hyg 1986; 80:642.
  85. Ohashi J, Naka I, Patarapotikul J, et al. Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection. Am J Hum Genet 2004; 74:1198.
  86. Nagel RL, Raventos-Suarez C, Fabry ME, et al. Impairment of the growth of Plasmodium falciparum in HbEE erythrocytes. J Clin Invest 1981; 68:303.
  87. Chotivanich K, Udomsangpetch R, Pattanapanyasat K, et al. Hemoglobin E: a balanced polymorphism protective against high parasitemias and thus severe P falciparum malaria. Blood 2002; 100:1172.
  88. Frischer H, Bowman J. Hemoglobin E, an oxidatively unstable mutation. J Lab Clin Med 1975; 85:531.
  89. Pasvol G, Weatherall DJ, Wilson RJ, et al. Fetal haemoglobin and malaria. Lancet 1976; 1:1269.
  90. Pasvol G, Weatherall DJ, Wilson RJ. Effects of foetal haemoglobin on susceptibility of red cells to Plasmodium falciparum. Nature 1977; 270:171.
  91. Friedman MJ. Oxidant damage mediates variant red cell resistance to malaria. Nature 1979; 280:245.
  92. Shear HL, Grinberg L, Gilman J, et al. Transgenic mice expressing human fetal globin are protected from malaria by a novel mechanism. Blood 1998; 92:2520.
  93. Kaul DK, Nagel RL, Llena JF, Shear HL. Cerebral malaria in mice: demonstration of cytoadherence of infected red blood cells and microrheologic correlates. Am J Trop Med Hyg 1994; 50:512.
  94. Weatherall DJ, Clegg J. The Thalassaemias, Oxford University Press, 2002.
  95. Brittenham G, Lozoff B, Harris JW, et al. Thalassemia in southern India. Interaction of genes for beta+-, beta o-, and delta o beta o-thalassemia. Acta Haematol 1980; 63:44.
  96. Kulozik AE, Kar BC, Serjeant GR, et al. The molecular basis of alpha thalassemia in India. Its interaction with the sickle cell gene. Blood 1988; 71:467.
  97. Labie D, Srinivas R, Dunda O, et al. Haplotypes in tribal Indians bearing the sickle gene: evidence for the unicentric origin of the beta S mutation and the unicentric origin of the tribal populations of India. Hum Biol 1989; 61:479.
  98. Modiano G, Morpurgo G, Terrenato L, et al. Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population. Am J Hum Genet 1991; 48:390.
  99. Terrenato L, Shrestha S, Dixit KA, et al. Decreased malaria morbidity in the Tharu people compared to sympatric populations in Nepal. Ann Trop Med Parasitol 1988; 82:1.
  100. Siniscalco M, Bernini L, Latte B, Motulski AG. Favism and thalassaemia in Sardinia and their relationship to malaria. Nature 1961; 190:1179.
  101. Hill AV, Bowden DK, O'Shaughnessy DF, et al. Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C). Blood 1988; 72:9.
  102. Flint J, Hill AV, Bowden DK, et al. High frequencies of alpha-thalassaemia are the result of natural selection by malaria. Nature 1986; 321:744.
  103. Yenchitsomanus P, Summers KM, Board PG, et al. Alpha-thalassemia in Papua New Guinea. Hum Genet 1986; 74:432.
  104. Enevold A, Alifrangis M, Sanchez JJ, et al. Associations between alpha+-thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania. J Infect Dis 2007; 196:451.
  105. Atamna H, Ginsburg H. The malaria parasite supplies glutathione to its host cell--investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. Eur J Biochem 1997; 250:670.
  106. Allison AC, Eugui EM. A radical interpretation of immunity to malaria parasites. Lancet 1982; 2:1431.
  107. Allison AC, Eugui EM. The role of cell-mediated immune responses in resistance to malaria, with special reference to oxidant stress. Annu Rev Immunol 1983; 1:361.
  108. Glushakova S, Balaban A, McQueen PG, et al. Hemoglobinopathic erythrocytes affect the intraerythrocytic multiplication of Plasmodium falciparum in vitro. J Infect Dis 2014; 210:1100.
  109. Roth EF Jr, Raventos-Suarez C, Rinaldi A, Nagel RL. Glucose-6-phosphate dehydrogenase deficiency inhibits in vitro growth of Plasmodium falciparum. Proc Natl Acad Sci U S A 1983; 80:298.
  110. Brockelman CR, Wongsattayanont B, Tan-ariya P, Fucharoen S. Thalassemic erythrocytes inhibit in vitro growth of Plasmodium falciparum. J Clin Microbiol 1987; 25:56.
  111. Pattanapanyasat K, Yongvanitchit K, Tongtawe P, et al. Impairment of Plasmodium falciparum growth in thalassemic red blood cells: further evidence by using biotin labeling and flow cytometry. Blood 1999; 93:3116.
  112. Roth EF Jr, Shear HL, Costantini F, et al. Malaria in beta-thalassemic mice and the effects of the transgenic human beta-globin gene and splenectomy. J Lab Clin Med 1988; 111:35.
  113. Udomsangpetch R, Sueblinvong T, Pattanapanyasat K, et al. Alteration in cytoadherence and rosetting of Plasmodium falciparum-infected thalassemic red blood cells. Blood 1993; 82:3752.
  114. Penman BS, Pybus OG, Weatherall DJ, Gupta S. Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean. Proc Natl Acad Sci U S A 2009; 106:21242.
  115. Allen SJ, O'Donnell A, Alexander ND, et al. alpha+-Thalassemia protects children against disease caused by other infections as well as malaria. Proc Natl Acad Sci U S A 1997; 94:14736.
  116. Mockenhaupt FP, Ehrhardt S, Gellert S, et al. Alpha(+)-thalassemia protects African children from severe malaria. Blood 2004; 104:2003.
  117. Williams TN, Wambua S, Uyoga S, et al. Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya. Blood 2005; 106:368.
  118. Enevold A, Lusingu JP, Mmbando B, et al. Reduced risk of uncomplicated malaria episodes in children with alpha+-thalassemia in northeastern Tanzania. Am J Trop Med Hyg 2008; 78:714.
  119. Wambua S, Mwangi TW, Kortok M, et al. The effect of alpha+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS Med 2006; 3:e158.
  120. Clegg JB, Weatherall DJ. Thalassemia and malaria: new insights into an old problem. Proc Assoc Am Physicians 1999; 111:278.
  121. Williams TN, Maitland K, Bennett S, et al. High incidence of malaria in alpha-thalassaemic children. Nature 1996; 383:522.
  122. Ifediba TC, Stern A, Ibrahim A, Rieder RF. Plasmodium falciparum in vitro: diminished growth in hemoglobin H disease erythrocytes. Blood 1985; 65:452.
  123. Krause MA, Diakite SA, Lopera-Mesa TM, et al. α-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected erythrocytes. PLoS One 2012; 7:e37214.
  124. Fowkes FJ, Allen SJ, Allen A, et al. Increased microerythrocyte count in homozygous alpha(+)-thalassaemia contributes to protection against severe malarial anaemia. PLoS Med 2008; 5:e56.
  125. Veenemans J, Andang'o PE, Mbugi EV, et al. Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya. J Infect Dis 2008; 198:401.
  126. Atkinson SH, Uyoga SM, Nyatichi E, et al. Epistasis between the haptoglobin common variant and α+thalassemia influences risk of severe malaria in Kenyan children. Blood 2014; 123:2008.