Having one copy of the sickle cell gene may help protect you from a malaria infection. But two copies of the gene may increase your risk of death from malaria.

Malaria is a potentially life threatening condition. Mosquitoes infected with a parasite called Plasmodium transmit malaria through their bites.

When an infected mosquito bites you, it releases the Plasmodium parasites into your bloodstream. They infect and damage your red blood cells (RBCs), which causes dangerous malaria symptoms.

Malaria is most common in sub-Saharan Africa. But it also occurs in parts of Central and South America and Southeast Asia.

Over time, some RBC conditions have evolved to protect against malaria. Sickle cell trait (SCT) is one such condition. It arises from a gene mutation for hemoglobin, the oxygen-carrying component of RBCs. But the same protection does not exist for people with sickle cell disease (SCD), those with two copies of the gene mutation.

Keep reading to learn about the unique link between malaria, sickle cell, and other RBC conditions.

Scientists first proposed a link between sickle cell and malaria in the late 1940s. They noticed that parts of the world with high rates of malaria overlapped with those with a high likelihood of sickle cell mutations.

Doctors noticed that people with hemoglobin sickle cell mutations could clear malaria parasites from their bodies much faster than those without these mutations. Why? Scientists are still working on piecing together the exact mechanism, but they have identified several key steps:

  1. Sickle cell mutations in hemoglobin make RBCs sickle-shaped. This causes them to be ineffective in doing their job of carrying blood oxygen. If you have these mutations, your body is used to detecting and destroying misshapen RBCs.
  2. When the malaria parasite enters your body, it infects RBCs. Sickle-shaped RBCs create a very hostile environment for the parasite’s growth, partially due to low oxygen levels.
  3. Decreased parasite growth may allow more time for the immune system to react and destroy the infected RBCs.

Sickle cell trait: A balanced polymorphism

Sickle cell conditions are a classic example of balanced polymorphism.

In humans, each gene contains two copies (alleles), one inherited from each parent. Mutations can affect one allele or both. In some genetic conditions, like SCD, these mutations can have a detrimental effect.

When both copies of a gene are affected, this causes you to have a dangerous, often life threatening condition. But if only one copy is affected, it sometimes can create a certain health benefit. This situation is called balanced polymorphism.

When it comes to sickle cell conditions, one affected copy is responsible for SCT, which protects against malaria. If both copies are affected, this results in SCD, a dangerous blood disorder.

Having different copies of the gene may give you a survival advantage in regions where malaria is common. This allows the affected gene to continue being more common in a community.

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People with SCT have one copy of a faulty hemoglobin gene, inherited from one of their parents. They don’t develop SCD, but they are carriers for the gene that causes the condition.

Having SCT does protect against malaria. In fact, according to the CDC, SCT provides 60% protection against the overall risk of death, especially in babies.

The mechanism by which SCT protects against malaria may also work in people with SCD. However, the risks associated with having SCD far outweigh this benefit.

People with sickle cell anemia (SCA), the most severe form of SCD, can often have a greater risk of death from malaria, compared with people who have SCT or no hemoglobin gene mutation. This is because malaria can trigger a sickle cell crisis.

A sickle cell crisis due to malaria can result in:

SCD may prevent your spleen from working as well as it should. Your spleen helps you clear infections. A dysfunctional spleen could increase your risk of a malaria infection.

Results from a 2022 study in Uganda suggested that children with SCA are born with certain protections against severe malaria. But researchers also found that even low levels of infection in children with SCA could lead to severe symptoms.

Thalassemia is a group of genetic disorders that also affect your hemoglobin. People with thalassemia have a mutation in one or both copies of their alpha-globin genes (in alpha-thalassemia) or beta-globin genes (in beta-thalassemia). Alpha-globins and beta-globins are subunits of hemoglobin.

Thalassemias are highly common in Southeast Asia, where malaria is also common.

According to a 2021 report, thalassemias may offer some protection against malaria. Alpha-thalassemia provides the most benefit without major adverse effects on health. But beta-thalassemia can carry significant risks and complications, especially when both beta-globin gene copies are affected.

Up until recently, there was no vaccine to prevent malaria. But in 2021, the World Health Organization began recommending a new malaria vaccine for children who live in sub-Saharan Africa and other parts of the world where the condition is common.

If you need to travel to an area with high occurrences of malaria, consult a doctor before the trip. It’s best to do this at least 4 to 6 weeks before you travel. Your doctor may prescribe you medication to reduce your risk of getting malaria.

If you travel or live in an area where malaria is common, be sure to do the following:

  • Regularly take any antimalarial medication a doctor prescribes.
  • Use insect repellent on your skin. Make sure it contains at least 50% DEET.
  • Sleep under mosquito nets treated with insecticide.
  • Wear long-sleeved shirts and pants that cover your arms and legs at night, when mosquitoes are most active.

If you’re not sure if malaria is common where you plan to travel, the CDC has an up-to-date map.

Both malaria and SCD are dangerous conditions that affect your RBCs. Malaria is an infectious condition you get from mosquito bites, but SCD is an inheritable genetic disorder.

Over time, SCT has evolved to protect against severe malaria infection. SCD may offer some protection against malaria as well, but the risks and complications of the disease itself outweigh this benefit.

Whether you have SCT or SCD, be sure to follow malaria prevention strategies if you live or travel in an area with high occurrences of malaria.