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How Sickle Cell Trait Resists Malaria

By Helen Anderson
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Sickle cell anemia disease is particularly common in Sub-Saharan Africans, South Americans, Caribbeans, Central Americans, Saudi Arabians, Indians, and people of Mediterranean descent. 1 out of every 500 Black or African American babies are born with the disease, as well as 1 out of every 36,000 Hispanic-American babies.

The gene responsible for the sickle cell trait is the Hemoglobin Beta gene, also known as HBB. It is a heterozygous gene found on the short arm of human chromosome 11. The normal form of this gene is Hb A, but there are many variants that can form as a result of a mutation of Hb A. The variant responsible for causing sickle cell anemia is Hb S. The disease is an autosomal recessive disorder, which means that it will only be expressed if a child inherits two copies of Hb S, one from each parent, or if a child inherits one copy of Hb S from one parent and another type of variant from the other parent. It will not be expressed if at least one normal copy (Hb A) is inherited from one parent. The genotype of someone who is only a carrier is HbAS.

Resistance of the Sickle Cell Trait to Malaria

Fortunately, there is great news for those who are only carriers of the trait (i.e. those with the HbAS genotype). Although the mechanism of protection is unknown, studies have shown that there is a high level of resistance to more complicated forms of malaria in HbAS individuals.

The first advantage Sickle Cell trait carriers have over those with the disease is a strong spleen that can destroy the Plasmodium Falciparum parasite, carried by female anopheles mosquitoes, which causes Malaria. The spleen has macrophages that can identify the Falciparum-infected sickle cells, and these macrophages swallow up the sickle cells in a process called phagocytosis, thereby eliminating them from the body. On the other hand, individuals with established Sickle Cell anemia develop what is called hyposplenism (reduced spleen function) or asplenia (no spleen function), and this leads to their acquisition of a more complicated form of Malaria.

The second advantage Sickle Cell trait carriers have is an acquired immune resistance to the malaria parasite. A study conducted in both Gambia and Sudan showed that HbAS individuals have an immune resistance against the Plasmodium Falciparum parasite. The way by which HbAS genes acquire such an immunity has been difficult to explain in medical literature due to the fact that there is no easy means to measure immunity to malaria.

Preventing and Treating Malaria in Patients with Sickle Cell Anemia

One way to prevent high-risk Sickle Cell disease patients from contracting malaria is to use constant prophylaxis (preventive measures)2 and management drugs which include the following:

  1. Hydroxyurea or Erythropoietin or Butyrate: The most common drug is hydroxyurea. These three drugs increase the production of hemoglobin in the body, thereby reducing the complications produced by sickled hemoglobin.
  2. Piracetam: The drug Piracetam helps to reverse the sickling of red blood cells in Sickle Cell anemia patients.4
  3. Clotrimazole: This drug causes depolymerization of the sickle red blood cells, reducing the number of dense cells.
  4. Blood transfusion: This is done in patients with extreme complications. It reduces the amount of Hb S red blood cells and hence reduces the complications.
  5. Hydration: Sickle red blood cells can obstruct blood vessels which leads to a decrease in body fluids. Hydration adds fluids to the body.
  6. Histone deacetylase inhibitors.
  7. Bone marrow transplant and gene therapy.


1. Sickle Cell Disease (SCD) [Internet]. Atlanta (GA): Center for Disease Control and Prevention; 2011 Sept 16. Available from: http://www.cdc.gov/ncbddd/sicklecell/data.html
2. Luzatto L. Sickle Cell Anaemia and Malaria. Mediterranean Journal of Hematology and Infectious Diseases [Internet]. 2012 Oct 3; 4(1): e2012065, DOI 10.4084/MJHID.2012.065. Available from: http://www.mjhid.org/article/view/10928/pdf
3. Williams TN, Mwangi TW, Roberts DJ, Alexander ND, Weatherall DJ, et al. An Immune Basis for Malaria Protection by the Sickle Cell Trait. PLoS Med [Internet]. 2005;2(5):e128, DOI:10.1371/journal.pmed.0020128
4. Mostafa HMA, et al. The Role of Piracetam in Treatment of Sickle Cell Anemia. National Journal of Physiology, Pharmacy, and Pharmacology [Internet]. 2012; 2(1):58-65. Available from: http://www.scopemed.org/?mno=9632

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