Relationship between sickle cell anemia and malaria

In my undergraduate teaching class, one of the most common query of students is; “Why do people with sickle cell anemia not get malaria”?

The above query is only partially right because:

  • Sickle cell hemoglobin confers a survival advantage against malaria. However, there is no clear cut understanding/postulates about how sickle cell anemia confers immunity against malaria.
  • People with sickle cell anemia do suffer from malaria, and very badly too. Malaria is the commonest cause of sickle cell crisis in Africa.

To understand the relationship between sickle cell anemia and malaria, one most have knowledge about sickle cell anemia and life cycle of malarial parasite and how the sickle cell shape of RBC may affect that life cycle of malarial parasite.

Sickle Cell Anemia

It is a serious blood disorder in which body makes sickle-shaped (crescent shaped) red blood cells (RBC).

Normal RBCs are disc-shaped and look like doughnuts without holes in the center. They move easily through blood vessels. Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle, or crescent, shape.

Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also raise the risk for infection.

As far as adult haemoglobin types are concerned when dealing with malaria, there are 3 broad phenotypes in adults

  • ‘AA’ : Normal population
  • ‘SS’ : Sickle Cell Anaemia
  • Sickle Cell Trait (genotype HbAS)
Sickle Cell Anemia
Sickle Cell Anemia

Only those individual that inherit two copies of the sickle mutation (one from their mother and the other from their father) develop sickle cell anemia. If untreated, these individuals have a shorter than normal life expectancy.


Life Cycle of Malaria and effect of Sickle cell trait

When female Anopheline mosquito bites a person and injects malarial parasites into the body, the malarial parasite (Plasmodium falciparum) first completes one cycle of Pre-Erythrocytic Schizogony in liver cells. Then it invades the RBCs and multiply within it until they burst, releasing more parasites (merozoites) into the body, to produce severe febrile illness with serious consequences.

In the sickle cell trait (AS), however, as soon as the malarial parasite  Plasmodium falciparum begins to multiply in the RBCs, using up the cell’s oxygen supply, the AS cell changes from round to sickle shape. Reduced oxygen levels result in diminished parasite growth. Apart from this, the malarial parasite cannot complete its life cycle due to cell sickling and destruction in RBCs (Erythrocytic Schizogony) preventing further progress of the disease.

Sickle Cell Trait and Resistance with Malaria

Malaria resistance by the sickle cell trait still remains the subject of considerable debate. Sickle cell trait (genotype HbAS) confers a high degree of resistance to severe and complicated malaria yet the precise mechanism remains unknown.

Individuals carrying just one copy of the sickle mutation- sickle cell trait (inherited from either father or mother) do not  develop sickle cell anemia and lead normal lives. However, it was found that these same individuals were in fact highly protected against malaria, thus explaining the high prevalence of this mutation in geographical areas where malaria is endemic.

Postulated Hypothesis (Research) for Resistance

  • Reduced ability of Plasmodium falciparum parasites to grow and multiply in HbAS erythrocytes
  • Parasite-infected HbAS RBCs tend to sickle, a process that may result in their premature destruction by the spleen
  • HbAS involves the enhancement of not only innate but also of acquired immunity to the parasite.
  • Sickle cell hemoglobin confers a survival advantage against malaria by inducing production of heme oxygenase-1 (HO-1) without affecting the normal infection cycle of malaria in RBCs.

In person suffering with sickle cell anemia (Homozygous SS Hemoglobin gene) the effects of fever, diarrhea, vomiting provoked a sickle crisis that cannot outweigh any beneficial effect of sickling-against-malarial-parasite.

To be a sickle cell trait (AS)  in a malarious environment appears to be better than not having sickle genes at all (AA), or having 2 sickle genes (SS).

Watch interactive Video: “Relation between Malaria and Sickle Cell Anemia

4 thoughts on “Relationship between sickle cell anemia and malaria

  1. Not to be rude, but CDC argues with you on how Sickle Cell sufferers ARE immune. Your article is very informative though I thank you. Anthony Allison had been studying this years, and scientists afterwards for decades to the present time. PS double edit your writing, there are several errors. Commonest is not proper grammar possibly most common for one example. 🙂

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