Document Type : Review Article


1 Department of zoology, Gombe State University, Gombe, Nigeria.

2 Department of zoology, Modibbo Adama University, Yola, Adamawa State, Nigeria

3 Department of Biomedical and Pharmaceutical Technology, Federal Polytechnic, Mubi, Nigeria


Human beings are sometime expose to the same to predisposing factors of a given infectious disease, but the outcome in terms of disease manifestation differs greatly. This variation is mainly attributed to the genetic makeup of such individuals; this is because human genetic has long been associated with the variation in susceptibility to various infectious diseases, which is termed as genetic resistance. Therefore the aim of this paper was to review the state of knowledge on genetic resistance associated with malaria infection. Genetic resistance to malaria can be describe as an inherited alteration or changes in the genetic material of humans specifically DNA molecule and other vital biomolecules which increases the chances of resistance to malaria and thus, result in an increased survival of individuals with those genetic alterations. In addition such changes also affect the general wellbeing and survival of the parasite to the extent that the parasite cannot even multiply or replicate itself while in such infected erythrocyte. This is because such alteration in the DNA molecule interferes with some of the vital chemical and biochemical processes of the parasite (Plasmodim spp). Therefore, several genetic disorders and or trait which include: Sickle cell disease, Glocose-6-Phosphatedehyrogenase deficiency, Pyruvate Kinase deficiency, Duffy antigen, Ovalocytocytosis, Thalassemia and ABO blood group are known to offer special protection against malaria disease in individuals who possessed at least one of such disorders or trait.

Graphical Abstract

Genetic resistance to human malaria


Main Subjects

Selected authors of this article by journal

Dr. Ismail Muhammad
Bala Abubakakar
Tanko Mahmoud Mohammad

Open Access

This article is licensed under a CC BY License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit:


Publisher’s Note

CMBR journal remains neutral with regard to jurisdictional claims in published maps and institutional afflictions.


Letters to Editor

Given that CMBR Journal's policy in accepting articles will be strict and will do its best to ensure that in addition to having the highest quality published articles, the published articles should have the least similarity (maximum 15%). Also, all the figures and tables in the article must be original and the copyright permission of images must be prepared by authors. However, some articles may have flaws and have passed the journal filter, which dear authors may find fault with. Therefore, the editor of the journal asks the authors, if they see an error in the published articles of the journal, to email the article information along with the documents to the journal office.

CMBR Journal welcomes letters to the editor ([email protected], [email protected]) for the post-publication discussions and corrections which allows debate post publication on its site, through the Letters to Editor. Critical letters can be sent to the journal editor as soon as the article is online. Following points are to be considering before sending the letters (comments) to the editor.

[1] Letters that include statements of statistics, facts, research, or theories should include appropriate references, although more than three are discouraged.

[2] Letters that are personal attacks on an author rather than thoughtful criticism of the author’s ideas will not be considered for publication.

[3] There is no limit to the number of words in a letter.

[4] Letter writers should include a statement at the beginning of the letter stating that it is being submitted either for publication or not.

[5] Anonymous letters will not be considered.

[6] Letter writers must include Name, Email Address, Affiliation, mobile phone number, and Comments.

[7] Letters will be answered as soon as possible.

  1. Winn ME, Zapala MA, Hovatta I, Risbrough VB, Lillie E, Schork NJ (2010) The effects of globin on microarray-based gene expression analysis of mouse blood. Mammalian Genome 21(5):268-275. doi:
  2. Hernandez-Valladares M, Rihet P, Iraqi FA (2014) Host susceptibility to malaria in human and mice: compatible approaches to identify potential resistant genes. Physiological genomics 46(1):1-16. doi:
  3. Faik I, van Tong H, Lell B, Meyer CG, Kremsner PG, Velavan TP (2017) Pyruvate kinase and Fcγ receptor gene copy numbers associated with malaria phenotypes. The Journal of infectious diseases 216(2):276-282. doi:
  4. Eridani S (2011) Sickle cell protection from malaria. Hematology reports 3(3):e24. doi:
  5. Van Zwieten R, Verhoeven AJ, Roos D (2014) Inborn defects in the antioxidant systems of human red blood cells. Free Radical Biology and Medicine 67:377-386. doi:
  6. Martinez J, Showering A, Oke C, Jones RT, Logan JG (2021) Differential attraction in mosquito–human interactions and implications for disease control. Philosophical Transactions of the Royal Society B 376(1818):20190811. doi:
  7. Davidson G, Chua TH, Cook A, Speldewinde P, Weinstein P (2019) Defining the ecological and evolutionary drivers of Plasmodium knowlesi transmission within a multi-scale framework. Malaria journal 18(1):1-13. doi:
  8. Kimura M, Soemantri A, Ishida T (2002) Malaria species and Southeast Asian ovalocytosis defined by a 27-bp deletion in the erythrocyte band 3 gene. Southeast Asian Journal of Tropical Medicine and Public Health 33(1):4-6
  9. Rockett KA, Clarke GM, Fitzpatrick K, Hubbart C, Jeffreys AE, Rowlands K, Craik R, Jallow M, Conway DJ, Bojang KA, Pinder M, Usen S, Sisay-Joof F, Sirugo G, Toure O, Thera MA, Konate S, Sissoko S, Niangaly A, Poudiougou B, Mangano VD, Bougouma EC, Sirima SB, Modiano D, Amenga-Etego LN, Ghansah A, Koram KA, Wilson MD, Enimil A, Evans J, Amodu O, Olaniyan S, Apinjoh T, Mugri R, Ndi A, Ndila CM, Uyoga S, Macharia A, Peshu N, Williams TN, Manjurano A, Riley E, Drakeley C, Reyburn H, Nyirongo V, Kachala D, Molyneux M, Dunstan SJ, Phu NH, Quyen NTN, Thai CQ, Hien TT, Manning L, Laman M, Siba P, Karunajeewa H, Allen S, Allen A, Davis TME, Michon P, Mueller I, Green A, Molloy S, Johnson KJ, Kerasidou A, Cornelius V, Hart L, Vanderwal A, SanJoaquin M, Band G, Le SQ, Pirinen M, Sepúlveda N, Spencer CCA, Clark TG, Agbenyega T, Achidi E, Doumbo O, Farrar J, Marsh K, Taylor T, Kwiatkowski DP, Malaria Genomic Epidemiology N (2014) Reappraisal of known malaria resistance loci in a large multicenter study. Nature genetics 46(11):1197-1204. doi:
  10. Withrock IC, Anderson SJ, Jefferson MA, McCormack GR, Mlynarczyk GS, Nakama A, Lange JK, Berg CA, Acharya S, Stock ML, Lind MS, Luna KC, Kondru NC, Manne S, Patel BB, De la Rosa BM, Huang KP, Sharma S, Hu HZ, Carlson SA (2015) Genetic diseases conferring resistance to infectious diseases. Genes & diseases 2(3):247-254. doi:
  11. Gai PP, van Loon W, Siegert K, Wedam J, Kulkarni SS, Rasalkar R, Boloor A, Kumar A, Jain A, Mahabala C, Baliga S, Devi R, Shenoy D, Gai P, Mockenhaupt FP (2019) Duffy antigen receptor for chemokines gene polymorphisms and malaria in Mangaluru, India. Malaria journal 18(1):328. doi:
  12. Damena D, Denis A, Golassa L, Chimusa ER (2019) Genome-wide association studies of severe P. falciparum malaria susceptibility: progress, pitfalls and prospects. BMC medical genomics 12(1):1-14. doi:
  13. Damena D, Denis A, Golassa L, Chimusa ER (2018) Genome-Wide Association Studies of malaria susceptibility and resistance: progress, pitfalls and prospects. BioRxiv):456707. doi:
  14. Fazeli-Nasab B (2021) Biological Evaluation of Coronaviruses and the Study of Molecular Docking, Linalool, and Thymol as orf1ab Protein Inhibitors and the Role of SARS-CoV-2 Virus in Bioterrorism. journal of ilam university of medical sciences 28(6):77-96. doi:
  15. Fazeli-Nasab B (2021) In Silico Analysis of the Effect of Scrophularia striata Linalool on VacA Protein of Helicobacter Pylori. scientific journal of ilam university of medical sciences 29(1):50-64. doi:
  16. Waitumbi JN, Kifude CM, Hunja CW, Ogutu BR (2018) Females of HbAS genotype have reduced concentration of the malaria protective deoxyhemoglobin S than males. PloS one 13(9):e0203455. doi:
  17. Eleonore NLE, Cumber SN, Charlotte EE, Lucas EE, Edgar MML, Nkfusai CN, Geh MM, Ngenge BM, Bede F, Fomukong NH, Kamga HLF, Mbanya D (2020) Malaria in patients with sickle cell anaemia: burden, risk factors and outcome at the Laquintinie hospital, Cameroon. BMC infectious diseases 20(1):40. doi:
  18. Elguero E, Délicat-Loembet LM, Rougeron V, Arnathau C, Roche B, Becquart P, Gonzalez J-P, Nkoghe D, Sica L, Leroy EM (2015) Malaria continues to select for sickle cell trait in Central Africa. Proceedings of the National Academy of Sciences 112(22):7051-7054. doi:
  19. Enevold A, Alifrangis M, Sanchez JJ, Carneiro I, Roper C, Børsting C, Lusingu J, Vestergaard LS, Lemnge MM, Morling N (2007) Associations between α+-thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania. The Journal of infectious diseases 196(3):451-459. doi:
  20. Dada-Adegbola HO, Brown BJ, Labaeka AA (2018) Prevalence of malaria and performance of a rapid diagnostic test for malaria in febrile children with sickle cell disease. Pediatric Hematology Oncology Journal 3(2):42-45. doi:
  21. David AN, Jinadu MY, Wapmuk AE, Gbajabiamila TA, Okwuzu JO, Herbertson EC, Ezechi OC (2018) Prevalence and impact of sickle cell trait on the clinical and laboratory parameters of HIV infected children in Lagos, Nigeria. Pan African Medical Journal 31(1):1-11. doi:
  22. Bunn HF (2013) The triumph of good over evil: protection by the sickle gene against malaria. Blood, The Journal of the American Society of Hematology 121(1):20-25. doi:
  23. Uyoga S, Macharia AW, Ndila CM, Nyutu G, Shebe M, Awuondo KO, Mturi N, Peshu N, Tsofa B, Scott JAG (2019) The indirect health effects of malaria estimated from health advantages of the sickle cell trait. Nature communications 10(1):1-7. doi:
  24. Booth C, Inusa B, Obaro SK (2010) Infection in sickle cell disease: a review. International Journal of Infectious Diseases 14(1):e2-e12. doi:
  25. Houwing M, De Pagter P, Van Beers E, Biemond B, Rettenbacher E, Rijneveld A, Schols E, Philipsen J, Tamminga R, van Draat KF (2019) Sickle cell disease: clinical presentation and management of a global health challenge. Blood reviews 37:100580. doi:
  26. Luzzatto L (2012) Sickle cell anaemia and malaria. Mediterranean journal of hematology and infectious diseases 4(1). doi:
  27. Makani J, Komba AN, Cox SE, Oruo J, Mwamtemi K, Kitundu J, Magesa P, Rwezaula S, Meda E, Mgaya J (2010) Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood, The Journal of the American Society of Hematology 115(2):215-220. doi:
  28. Archer NM, Petersen N, Clark MA, Buckee CO, Childs LM, Duraisingh MT (2018) Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition. Proceedings of the National Academy of Sciences 115(28):7350-7355. doi:
  29. Otoikhian C, Okoror L (2012) Sickle cell disease african killer: biologists alternative. Int J Pharma Med Biol Sci 1(2):232-245
  30. Catherine B, Baba I, Stephen K (2010) Infections in sickle cell disease. International Journal of Infectious Disease 14(1):2-12. doi:
  31. Cowman AF, Healer J, Marapana D, Marsh K (2016) Malaria: biology and disease. Cell 167(3):610-624. doi:
  32. Hannemann A, Rees D, Tewari S, Gibson J (2015) Cation homeostasis in red cells from patients with sickle cell disease heterologous for HbS and HbC (HbSC genotype). EBioMedicine 2(11):1669-1676. doi:
  33. Cytlak U, Hannemann A, Rees D, Gibson J (2013) Identification of the Ca2+ entry pathway involved in deoxygenation-induced phosphatidylserine exposure in red blood cells from patients with sickle cell disease. Pflügers Archiv-European Journal of Physiology 465(11):1651-1660. doi:
  34. Peters AL, Noorden CJV (2009) Glucose-6-phosphate dehydrogenase deficiency and malaria: cytochemical detection of heterozygous G6PD deficiency in women. Journal of Histochemistry & Cytochemistry 57(11):1003-1011. doi:
  35. Howes RE, Dewi M, Piel FB, Monteiro WM, Battle KE, Messina JP, Sakuntabhai A, Satyagraha AW, Williams TN, Baird JK (2013) Spatial distribution of G6PD deficiency variants across malaria-endemic regions. Malaria journal 12(1):1-15. doi:
  36. Moore LR, Fujioka H, Williams PS, Chalmers JJ, Grimberg B, Zimmerman PA, Zborowski M (2006) Hemoglobin degradation in malaria‐infected erythrocytes determined from live cell magnetophoresis. The FASEB Journal 20(6):747-749. doi:
  37. Vasquez M, Zuniga M, Rodriguez A (2021) Oxidative Stress and Pathogenesis in Malaria. Frontiers in cellular and infection microbiology 2021:1227. doi:
  38. Machado P, Manco L, Gomes C, Mendes C, Fernandes N, Salomé G, Sitoe L, Chibute S, Langa J, Ribeiro L (2012) Pyruvate kinase deficiency in sub-Saharan Africa: identification of a highly frequent missense mutation (G829A; Glu277Lys) and association with malaria. PLoS ONE 7(10). doi:
  39. Zanella A, Fermo E, Bianchi P, Chiarelli LR, Valentini G (2007) Pyruvate kinase deficiency: the genotype-phenotype association. Blood reviews 21(4):217-231. doi:
  40. Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M, Quirt I, Gros P, Kain KC (2008) Pyruvate kinase deficiency and malaria. New England Journal of Medicine 358(17):1805-1810. doi:
  41. Erhabor O, Shehu C, Alhaji Y, Yakubu A (2014) Duffy red cell phenotypes among pregnant women in Sokoto, North Western Nigeria. J Blood Disord Transfus 5:7-11. doi:
  42. Carvalho GBd, Carvalho GBd (2011) Duffy Blood Group System and the malaria adaptation process in humans. Revista brasileira de hematologia e hemoterapia 33(1):55-64. doi:
  43. Weber SS, Tadei WP, Martins AS (2012) Polymorphism of the Duffy blood group system influences the susceptibility to Plasmodium vivax infection in the specific area from Brazilian Amazon. Brazilian Journal of Pharmacy 93(1):33-37
  44. George MT, Schloegel JL, Ntumngia FB, Barnes SJ, King CL, Casey JL, Foley M, Adams JH (2019) Identification of an immunogenic broadly inhibitory surface epitope of the Plasmodium vivax Duffy binding protein ligand domain. Msphere 4(3):e00194-00119. doi:
  45. Patarroyo MA, Molina-Franky J, Gómez M, Arévalo-Pinzón G, Patarroyo ME (2020) Hotspots in plasmodium and RBC receptor-ligand interactions: Key pieces for inhibiting malarial parasite invasion. International Journal of Molecular Sciences 21(13):4729. doi:
  46. Kano FS, de Souza AM, de Menezes Torres L, Costa MA, Souza-Silva FA, Sanchez BAM, Fontes CJF, Soares IS, de Brito CFA, Carvalho LH (2018) Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria. Scientific reports 8(1):1-14. doi:
  47. Ménard D, Barnadas C, Bouchier C, Henry-Halldin C, Gray LR, Ratsimbasoa A, Thonier V, Carod J-F, Domarle O, Colin Y (2010) Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people. Proceedings of the National Academy of Sciences 107(13):5967-5971. doi:
  48. Golassa L, Amenga-Etego L, Lo E, Amambua-Ngwa A (2020) The biology of unconventional invasion of Duffy-negative reticulocytes by Plasmodium vivax and its implication in malaria epidemiology and public health. Malaria journal 19(1):1-10. doi:
  49. Isaac I, John R, Udomah F, Imoru M, Erhabor O, Femi A (2016) Duffy blood group distribution among patients in a malaria endemic region. Int J Trop Dis Health 19(3):29050. doi:
  50. Baranova A, Sergiev V, Morozova L, Turbabina N, Morozov E (2019) Imported plasmodium vivax malaria in the Russian federation from Western Sub-Saharan Africa. Journal of tropical medicine 2019(Article ID: 4610498). doi:
  51. Cavasini CE, de Mattos LC, Couto ÁADA, Couto VSDA, Gollino Y, Moretti LJ, Bonini-Domingos CR, Rossit AR, Castilho L, Machado RL (2007) Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region. Malaria journal 6(1):1-8. doi:
  52. Williams TN (2006) Human red blood cell polymorphisms and malaria. Current opinion in microbiology 9(4):388-394. doi:
  53. Messori C, Prinzera SV, di Bardone FB (2019) Deep into the water: exploring the hydro-electromagnetic and quantum-electrodynamic properties of interfacial water in living systems. Open Access Library Journal 6(5):Article ID: 92815. doi:
  54. Warncke JD, Beck H-P (2019) Host cytoskeleton remodeling throughout the blood stages of Plasmodium falciparum. Microbiology and Molecular Biology Reviews 83(4):e00013-00019. doi:
  55. Steensma DP, Hoyer JD, Fairbanks VF Hereditary red blood cell disorders in middle eastern patients. In: Mayo Clinic Proceedings, 2001. vol 3. Elsevier, pp 285-293. doi:
  56. Musallam KM, Rivella S, Vichinsky E, Rachmilewitz EA (2013) Non-transfusion-dependent thalassemias. haematologica 98(6):833. doi:
  57. Rattanapunya S, Kuesap J, Chaijaroenkul W, Rueangweerayut R, Na-Bangchang K (2015) Prevalence of malaria and HIV coinfection and influence of HIV infection on malaria disease severity in population residing in malaria endemic area along the Thai–Myanmar border. Acta tropica 145:55-60. doi:
  58. Roberts DJ, Williams TN (2003) Haemoglobinopathies and resistance to malaria. Redox Report 8(5):304-310. doi:
  59. Kuesap J, Chaijaroenkul W, Rungsihirunrat K, Pongjantharasatien K, Na-Bangchang K (2015) Coexistence of malaria and thalassemia in malaria endemic areas of Thailand. The Korean journal of parasitology 53(3):265. doi:
  60. Wambua S, Mwangi TW, Kortok M, Uyoga SM, Macharia AW, Mwacharo JK, Weatherall DJ, Snow RW, Marsh K, Williams TN (2006) The effect of α+-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya. PLoS medicine 3(5):e158. doi:
  61. Gong L, Parikh S, Rosenthal PJ, Greenhouse B (2013) Biochemical and immunological mechanisms by which sickle cell trait protects against malaria. Malaria journal 12(1):1-9. doi:
  62. LaMonte G, Philip N, Reardon J, Lacsina JR, Majoros W, Chapman L, Thornburg CD, Telen MJ, Ohler U, Nicchitta CV (2012) Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance. Cell host & microbe 12(2):187-199. doi:
  63. Afoakwah R, Aubyn E, Prah J, Nwaefuna EK, Boampong JN (2016) Relative susceptibilities of ABO blood groups to Plasmodium falciparum malaria in Ghana. Advances in Hematology 2016:Article ID: 5368793. doi:
  64. Cserti CM, Dzik WH (2007) The ABO blood group system and Plasmodium falciparum malaria. Blood, The Journal of the American Society of Hematology 110(7):2250-2258. doi:
  65. Gomerep SS, Terver AM, Oye IH (2017) Prevalence of malaria parasitaemia and its association with ABO blood group in Jos, Nigeria. International Journal of Infectious Diseases and Therapy 2(3):59-65. doi:
  66. Panda AK, Panda SK, Sahu AN, Tripathy R, Ravindran B, Das BK (2011) Association of ABO blood group with severe falciparum malaria in adults: case control study and meta-analysis. Malaria journal 10(1):1-8. doi:
  67. Barragan A, Kremsner PG, Wahlgren M, Carlson J (2000) Blood group A antigen is a coreceptor in Plasmodium falciparum rosetting. Infection and immunity 68(5):2971-2975. doi:
  68. Tekeste Z, Petros B (2010) The ABO blood group and Plasmodium falciparum malaria in Awash, Metehara and Ziway areas, Ethiopia. Malaria journal 9(1):1-4. doi:
  69. Hegde S, Sinha R, Chakraborti S, Ojha L (2015) Relationship between malaria and ABO blood group types. International Journal of Science and Research 5(5):1041-1044. doi:
  70. Rowe JA, Handel IG, Thera MA, Deans A-M, Lyke KE, Koné A, Diallo DA, Raza A, Kai O, Marsh K (2007) Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting. Proceedings of the National Academy of Sciences 104(44):17471-17476. doi: