Sickle Cell and Malaria: What’s the Link?

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Malaria is a potentially life-threatening disease caused by a parasite from the Plasmodium genus. This parasite is spread through the bite of a female Anopheles mosquito. Malaria is most likely to be found in sub-Saharan Africa, though it can also be found in parts of Central and South America and Southeast Asia.

While five species of Plasmodium can infect humans, most malarial infections are caused by Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P. vivax). There were over 240 million malaria cases worldwide in 2020, and more than 600,000 people died from malaria that year.

Over time, some red blood cell disorders have evolved to help reduce the severity of malaria. One of these red blood cell disorders is sickle cell trait, in which a person produces both normal hemoglobin and abnormal hemoglobin. Hemoglobin is the molecule that carries oxygen in red blood cells (RBCs).

This article will review the connection between sickle cell trait and how it protects against malaria.

Woman and child in Africa where malaria and sickle cell trait are both common

Avatar_023 / Getty Images


After someone is bitten by an infected mosquito, the malaria parasite moves into the liver and infects liver cells. After these cells rupture, the parasite infects red blood cells.

These infected red blood cells travel through the blood vessels. The parasites turn the cells' oxygen-transporting protein hemoglobin into a toxic form. When the RBCs burst, they dump wastes and toxins into the blood. These can cause significant symptoms in an affected person, which can lead to death if untreated.

Malaria can’t be spread from person to person by close contact or through the air. However, because the parasite is present in blood cells, it is possible that malaria can be transmitted through a blood donation or the sharing of needles from an infected person.

Sickle Cell Disease

Sickle cell disease is an inherited genetic disorder that affects the hemoglobin molecule in red blood cells. The gene produces abnormal hemoglobin called hemoglobin S.

As it is a recessive inherited disorder, someone must get one copy of the sickle cell gene from each parent to have sickle cell disease, in which the person only produces abnormal hemoglobin.

If someone receives a normal copy from one parent but an abnormal copy from the other, they have sickle cell trait. They produce both normal and abnormal hemoglobin.

Hemoglobin in RBCs transports oxygen from the lungs throughout the body. In the small blood vessels, hemoglobin releases oxygen and binds carbon dioxide. When the blood returns to the lungs, hemoglobin exchanges carbon dioxide for oxygen.

Normally, red blood cells are disk-shaped and flexible, allowing them to travel through small blood vessels. In sickle cell disease, hemoglobin S causes problems when the oxygen concentration in the cell is low (such as in the small blood vessels). It makes the RBC sticky, rigid, and forms a sickle shape.

Sickle cells can clog small blood vessels. They also die early. Symptoms and complications of sickle cell disease include:

  • Anemia (a low number of healthy red blood cells)
  • Fever
  • Severe pain
  • Stroke (a blockage of blood flow or bleeding in the brain)
  • Liver disease
  • Blood clots

Why the Sickle Cell Trait Remains in the Human Population

People with sickle cell trait often do not have the symptoms of sickle cell disease because they produce enough normal hemoglobin in addition to the abnormal hemoglobin. However, they can pass the sickle cell gene on to their children.

People living with the sickle cell trait have shown some resistance to severe forms of malaria. A high number of people have sickle cell trait in areas of the world where malaria is most commonly found. This protection against malaria has kept the sickle cell gene mutation in the population.

How Common Is Sickle Cell Trait?

Sickle cell trait is found in up to 3 million Americans and up to 10% of African Americans. It can also be found at a higher prevalence than in the general population in people with Hispanic, southern European, and Middle Eastern ancestry.

The History of Sickle Cell and Malaria

There is significant overlap in the locations where sickle cell mutations and malaria are found. The areas in the world that have high malaria rates are the same as those with high rates of sickle cell mutations.

Although it is estimated that malaria and sickle cell trait have existed for at least 5,000 years, over time, the gene associated with sickle cell trait (HBB) has mutated to be more protective against malaria. The connection between sickle cell trait and malaria was first discovered in the 1940s.

Studies of the genetics of malaria and sickle cell have shown the evolution over time from its origins in southern Africa and how it has spread across Africa and the globe.

How Does Sickle Cell Protect Against Malaria?

People living with sickle cell trait have a significant reduction in the number of malarial parasites living in the body. Children with sickle cell trait and malaria can clear the infection much quicker than those without sickle cell trait.

It has not been determined exactly how sickle cell trait protects against malaria. Many reasons are likely, not just one. Theories coming from research studies into why sickle cell trait protects against malaria are:

  • The infected RBCs will sickle and then be destroyed by the spleen (an organ that filters the blood).
  • Lower oxygen states due to hemoglobin S in infected cells interfere with parasite growth.
  • In those with sickle cell trait, the infected RBC isn’t able to stick as easily to the walls of the blood vessel, which is one of the ways malaria causes illness.
  • Decreased parasite growth may allow more time for the immune system to react to and destroy the infected RBCs.


Although sickle cell disease is often linked to severe side effects and complications, those living with sickle cell trait may have an advantage regarding malaria. The sickle cell trait is inherited when someone inherits one copy of the mutated gene. This one copy doesn’t cause sickle cell disease but can give some protection against malaria.

The areas of the world with the highest malaria rates also have the highest rates of sickle cell trait. 

A Word From Verywell

Malaria is a very serious and life-threatening illness that affects millions of people worldwide. Although much less common in the United States, it can still be an issue if people travel to areas of the world that have high rates of malaria.

If you plan to travel to these high-risk countries, talk to your healthcare provider about what you can do to keep yourself safe.

Frequently Asked Questions

  • Why is sickle cell more common in Africa?

    The sickle cell mutation can offer protection against malaria. Malaria is much more common in Africa. Having sickle cell trait usually does not result in illness, but can enable a person to survive malaria to reproduce and pass the trait on to their children. Over time, this has resulted in the sickle cell mutation being more common in people in Africa.

  • How is sickle cell anemia inherited?

    Sickle cell anemia has an autosomal recessive inheritance. This means that for someone to be diagnosed with sickle cell anemia, they must get a mutated copy of the gene from each parent.

  • What does it mean to have sickle cell trait?

    Sickle cell trait means that someone inherits only one copy of the mutated gene. This does not give them sickle cell anemia, and it can offer them protection against malaria.

    They can pass the mutated gene to their children, although each child has only a 50% chance of receiving a mutated gene from the parent with sickle cell trait.

10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Centers for Disease Control and Prevention. Malaria: frequently asked questions (FAQs).

  2. Centers for Disease Control and Prevention. Malaria: biology.

  3. Centers for Disease Control and Prevention. Malaria: disease.

  4. Centers for Disease Control and Prevention. What is sickle cell trait?

  5. Centers for Disease Control and Prevention. What is sickle cell disease?

  6. Depetris-Chauvin E, Weil DN. Malaria and early African development: evidence from the sickle cell traitEcon J (London). 2018;128(610):1207-1234. doi:10.1111/ecoj.12433

  7. American Society of Hematology. Sickle cell trait.

  8. Esoh K, Wonkam A. Evolutionary history of sickle-cell mutation: implications for global genetic medicine. Hum Mol Genet. 2021;30(R1):R119-R128. doi:10.1093/hmg/ddab004

  9. Archer NM, Petersen N, Clark MA, Buckee CO, Childs LM, Duraisingh MT. Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition. Proc Natl Acad Sci U S A. 2018;115(28):7350-7355. doi:10.1073/pnas.1804388115

  10. Kariuki SN, Williams TN. Human genetics and malaria resistanceHum Genet. 2020;139(6):801-811. doi:10.1007/s00439-020-02142-6

By Julie Scott, MSN, ANP-BC, AOCNP
Julie is an Adult Nurse Practitioner with oncology certification and a healthcare freelance writer with an interest in educating patients and the healthcare community.