Sickle Cell Trait and Protection Against Malaria: Review Literature
DOI:
https://doi.org/10.33096/gmj.v7i1.134Keywords:
Malaria, sickle cell trait (HbAS), protectionAbstract
Introduction: Malaria is an infectious illness caused by various Plasmodium parasites transmitted by Anopheles mosquitoes. Currently, malaria is still a health problem with a significant incidence globally and has high morbidity and mortality. This makes researchers continue to seek solutions for malaria eradication. One of the things that is known to be protective against severe malaria infection is the sickle cell trait or HbAS.
Content: Sickle cell trait is a condition in which an individual is a carrier or has a single gene that causes sickle cell disease. The way sickle cell trait protects against malaria has been suggested for a long time. Along with the development of science and technology, various mechanisms of how the sickle cell trait protects against severe malaria are becoming known. Several mechanisms include sickling, miRNA, decreased cytoadherence, and immunological mechanisms.
Conclusion: Malaria is most often caused by Plasmodium falciparum. Indonesia is still an endemic country with the most frequent cases of malaria in children. One thing that is known to be protective against severe malaria, both symptomatic and asymptomatic malaria, is the sickle cell trait with various underlying mechanisms.
References
Buck E, Finnigan NA. Malaria. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551711/
González-Sanz M, Berzosa P, Norman FF. Updates on Malaria Epidemiology and Prevention Strategies. Current Infectious Disease Reports 2023;25(7):131–139; doi: 10.1007/s11908-023-00805-9.
Archer NM, Petersen N, Clark MA, et al. Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition. Proceedings of the National Academy of Sciences of the United States of America 2018;115(28):7350–7355; doi: 10.1073/pnas.1804388115.
Ashorobi D, Ramsey A, Killeen RB, et al. Sickle Cell Trait. 2024.; doi: 10.1016/B978-1-4377-1720-4.00296-X.
Chauvet M, Chhuon C, Lipecka J, et al. Sickle Cell Trait Modulates the Proteome and Phosphoproteome of Plasmodium falciparum-Infected Erythrocytes. Frontiers in Cellular and Infection Microbiology 2021;11(March):1–15; doi: 10.3389/fcimb.2021.637604.
Cyrklaff M, Srismith S, Nyboer B, et al. Oxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes. Nature Communications 2016;7:1–11; doi: 10.1038/ncomms13401.
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(1):29–36; doi: 10.1016/j.ebiom.2014.10.006.
Lansche C. Protection against Severe Malaria by Hemoglobin S and C: A Quantitative Understanding of the Cytoadhesion Behavior of Plasmodium Falciparum Infected Erythrocytes. 2018.
Oxendine Harp K, Bashi A, Botchway F, et al. Sickle Cell Hemoglobin Genotypes Affect Malaria Parasite Growth and Correlate with Exosomal miR-451a and let-7i-5p Levels. International Journal of Molecular Sciences 2023;24(8):4–6; doi: 10.3390/ijms24087546.
Tambunan RTH. Dasar Imunitas Pada Proteksi Terhadap Malaria Oleh Sifat Sel Sabit. Majalah Ilmiah METHODA 2022;12(1):45–51; doi: 10.46880/methoda.vol12no1.pp45-51.
Gómez-Díaz E, Ranford-Cartwright L. Evolutionary race: Malaria evolves to evade sickle cell protection. Cell host & microbe 2022;30(2):139–141; doi: 10.1016/j.chom.2022.01.010.
Ngou CM, Bayibéki AN, Abate L, et al. Influence of the sickle cell trait on Plasmodium falciparum infectivity from naturally infected gametocyte carriers. BMC Infectious Diseases 2023;23(1):1–11; doi: 10.1186/s12879-023-08134-x.
Elendu C, Amaechi DC, Alakwe-Ojimba CE, et al. Understanding Sickle cell disease: Causes, symptoms, and treatment options. Medicine (United States) 2023;102(38):E35237; doi: 10.1097/MD.0000000000035237.
Zekar L, Tariq Sharman. Plasmodium Falciparum Malaria. 2023.
Otoikhian C, Osakwe A, Utieyin M, et al. Malaria Resistance and Sickle Cell Trait: a Review. International Journal of Life Sciences Biotechnology and Pharma Research 2014;3(3):52–71.
Lansche C, Dasanna AK, Quadt K, et al. The sickle cell trait affects contact dynamics and endothelial cell activation in Plasmodium falciparum-infected erythrocytes. Communications Biology 2018;1(1):1–14; doi: 10.1038/s42003-018-0223-3.
Ademolue TW, Amodu OK, Awandare GA. Sickle cell trait is associated with controlled levels of haem and mild proinflammatory response during acute malaria infection. Clinical and Experimental Immunology 2017;188(2):283–292; doi: 10.1111/cei.12936.
Diakité SAS, 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. Malaria Journal 2016;15(1):1–10; doi: 10.1186/s12936-016-1522-0.
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 2013;12(2):187–199; doi: 10.1016/j.chom.2012.06.007.Translocation.
Petersen JEV, Saelens JW, Freedman E, et al. Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes. PLoS Pathogens 2021;17(6):1–11; doi: 10.1371/journal.ppat.1009659.
Loiseau C, Traore B, Ongoiba A, et al. Memory CD8+ T cell compartment associated with delayed onset of Plasmodium falciparum infection and better parasite control in sickle-cell trait children. Clinical and Translational Immunology 2021;10(3):1–12; doi: 10.1002/cti2.1265.






