Individuals who carry the sickle cell trait, a condition in which red blood cells are abnormally shaped, have always been highly protected against severe malaria.
However, new research by the Kenya Medical Research Institute shows the malaria parasite has adapted to overcome this protection.
The study, published in Nature, found variants of the malaria parasites that have evolved to infect and cause serious disease in people who carry sickle haemoglobin.
“In this study, we searched for an association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children ascertained with severe malaria due to Plasmodium falciparum,” the researchers said.
They found that malaria in children with sickle cell tended to be caused by a certain type of mutated parasite.
The researchers suggested that the sickle cell trait may have applied pressure on the plasmodium parasite over time, forcing it to adapt.
This led to a variant that can now infect people with sickle cell as well as those with normal red blood cells.
“We identified a strong association between sickle haemoglobin in the host and three regions of the parasite genome, that is not explained by population structure or other covariates, and that is replicated in additional samples,” the researchers said.
The study is titled "Malaria protection due to sickle haemoglobin depends on parasite genotype."
The researchers are from Kemri-Wellcome Trust Research Programme, Wellcome Sanger Institute, the University of Oxford, the MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine (LSHTM), along with collaborators from the US and Mali.
The scientists said this is the first time this phenomenon has been observed in a study and further research is needed to understand the biological mechanisms behind this.
Prof Tom Williams, a senior fellow at Kemri, said, “Previously, sickle haemoglobin was believed to have a protective effect against severe disease.
"However, this study highlights the importance of continually investigating this parasite so that we can be informed about how it adapts against selective pressures.”
Normal blood cells are disc-shaped while sickle cells are irregularly shaped. Individuals carrying just one copy of the sickle cell can lead normal lives and do not develop sickle cell anaemia.
Past research has confirmed these individuals are highly protected against severe malaria. This explained the high prevalence of sickle cell in geographical areas where malaria is endemic, such as western Kenya.
The sickle-shaped cells have porous membranes that leak nutrients that the malaria parasites need to survive and reproduce. The immune system then clears the infected cells before the parasite can complete its life cycle and infect other red blood cells.
Individuals, therefore, tend to get milder forms of malaria rather than the life-threatening kind that can afflict people with normal blood cells.
But from the Kemri study, the defiant malaria parasites are now overcoming this protection.
The researchers said understanding how this happens could lead to new ways to protect against and treat malaria.
“Greater clarity on the ways that P. falciparum evades the human body’s defences could lead to new opportunities for protecting against malaria and treating those living in the most affected areas,” Prof David Conway, the study author and professor of biology at LSHTM, said in a statement.
(Edited by Bilha Makokha)