Getting to grips with malaria
A genetic mutation that protects children against malaria’s effects on the brain may lead to new treatment strategies.
Malaria kills more than half a million children in Africa every year. The disease is caused by the Plasmodium falciparum parasite, and mosquitos infected with the parasites spread them to humans when they bite. Once inside a human, the parasites infect the red blood cells. In severe cases, these red blood cells can stick to the walls of small blood vessels that supply the brain and so hinder the flow of oxygen, causing a coma. This is called cerebral malaria. Malaria can also result in the destruction of many oxygen-carrying red blood cells, which causes severe anemia. Both cerebral malaria and severe anemia can lead to death.
Small changes (called mutations) in certain human genes can protect against malaria. Over time, mutations that protect people living in Africa from dying from malaria have been passed down through generations. A good example is the sickle cell mutation, which causes red blood cells to be of an unusual shape, but also affects the ability of malaria parasites to grow normally within red cells. Finding new mutations that protect against malaria may help scientists understand how severe malaria happens and eventually develop new drugs and vaccines against the disease. Some studies have found that mutations in a gene called complement receptor 1 (CR1) may be protective, although others have disagreed.
Now, Opi, Swann et al. show that children with one of the CR1 mutations were one-third less likely to get cerebral malaria and half as likely to die as children without the mutation. In the study, genetic and health information on more than 5,500 children in Kenya were analyzed to see if the severity of malaria differed depending on whether they had a CR1 mutation. They also found that the CR1 mutation is only protective against severe malaria when the child does not have another malaria- protective mutation called α-thalassemia. In children with α-thalassemia, the CR1 mutation does not make a difference.
The interaction between the CR1 mutation and α-thalassemia may explain why some studies did not show a benefit of CR1. If the researchers did not include α-thalassemia in their assessment, they could not have seen the whole picture. Future studies showing how the CR1 mutation protects against cerebral malaria could help identify new treatments that prevent severe disease or death. More study of interactions between genes that play a role in malaria may also be helpful.
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