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Research Article Volume 12 Issue 1
The protective role of sickle cell trait against plasmodium falciparum malaria
Moses Adondua Abah, Ezekiel Uduak Archibong, Micheal Abimbola Oladosu, Ezeudu Paschal Chikelum, Adaora Chiamaka Ekekwe, Silas Verwiyeh Tatah, Ayoade Babatunde Olanrewaju, Ochuele Dominic Agida
Received: November 28, 2025 | Published: December 8, 2025
Citation: Abah MA, Archibong EU, Oladosu MA, et al. The protective role of sickle cell trait against plasmodium falciparum malaria. J Hum Virol Retrovirol. 2025;12(1):23-31. DOI: 10.15406/jhvrv.2025.12.00283
Abstract
Malaria
caused by Plasmodium falciparum
remains a major global health burden, disproportionately affecting populations
in sub-Saharan Africa. Over millennia, the intense selective pressure exerted
by malaria has driven the emergence of human genetic adaptations that confer
partial resistance to infection. Among these, the sickle cell trait
(heterozygous HbAS) represents one of the most compelling examples of natural
protection against P. falciparum malaria. This review explores current
knowledge on the molecular, physiological, immunological, and evolutionary
mechanisms underlying this protection. At the genetic level, the β-globin gene
mutation leading to hemoglobin S alters erythrocyte physiology, impairing
parasite growth and promoting early clearance of infected cells.
Epidemiological studies consistently demonstrate that HbAS individuals
experience lower malaria incidence, reduced parasitemia, and diminished risk of
severe clinical manifestations such as cerebral malaria and severe anemia.
Mechanistically, factors such as intermittent sickling under hypoxic
conditions, increased oxidative stress, and altered cytoadherence impede
parasite maturation and sequestration. Moreover, HbAS erythrocytes modulate
innate and adaptive immune responses, enhancing macrophage activity and
cytokine balance, thereby limiting parasite proliferation and immunopathology.
From an evolutionary perspective, this heterozygote advantage exemplifies
balanced polymorphism, wherein malaria resistance maintains the deleterious HbS
allele in endemic populations. Understanding these multifactorial protective
pathways not only illuminates gene–environment co-evolution but also provides a
foundation for novel therapeutic strategies, including host-directed
antimalarial interventions and precision medicine in endemic regions. This
review integrates genetic, biochemical, immunological, and epidemiological
insights to underscore the enduring biomedical significance of the sickle
cell–malaria relationship.
Keywords: Plasmodium falciparum, sickle cell trait, hemoglobin S, malaria resistance, balanced polymorphism and immunohematology.
©2025 Abah, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.