Regenerative
Sickle cell trait shapes which malaria parasites can infect you, study finds
By Life and Health Today Staff, . Life and Health Today.
People carrying the sickle cell trait are just as likely to be infected by the malaria parasite Plasmodium falciparum as people without it, but they are a tenth as likely to develop symptomatic disease. A new study published in Nature Microbiology now offers a partial explanation: the parasites that infect sickle cell trait carriers are, almost exclusively, a genetically distinct variety from those that infect everyone else.
Researchers analyzed the genetics of 2,246 healthy schoolchildren in Mfou, a region of high malaria transmission in Cameroon, along with the malaria parasites found in those children. The work was led by Sandrine Nsango, described by Genetic Engineering and Biotechnology News as an associate professor of molecular biology at the University of Douala and a researcher at the Centre Pasteur du Cameroun. The findings were published in Nature Microbiology under the title "Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections."
Sickle cell trait means carrying one copy of the genetic variant that, in two copies, causes sickle cell disease. That single copy changes the shape of hemoglobin, the protein in red blood cells that carries oxygen, in a way that has long been known to reduce the severity of malaria. What has been less clear is exactly how.
The study focused on asymptomatic infections, meaning cases where the parasite is present but the person feels no symptoms. That matters because, according to Genetic Engineering and Biotechnology News, asymptomatic infections were extremely common in this population, affecting three-quarters of the healthy children studied. Among the 1,701 asymptomatic infections analyzed, children with and without the sickle cell variant were infected at similar overall rates. But the parasite genotypes doing the infecting differed sharply between the two groups.
Children carrying the sickle cell variant were strongly associated with parasites carrying what the researchers call Pfsa-positive alleles, specific genetic variants at two locations in the parasite genome labeled Pfsa1 and Pfsa3. These variants had previously been identified in the rarer cases where sickle cell trait carriers do develop symptomatic malaria, suggesting they may give the parasite some ability to survive in sickle cell hemoglobin. The new study extends that observation to the much larger pool of asymptomatic infections.
"Sickle cell trait may protect against malaria, not only by changing how the human host responds to infection, but also by shaping which parasites are able to survive and establish infection," Nsango said, as quoted by Genetic Engineering and Biotechnology News.
What this does not show is whether the Pfsa-positive parasite variants are themselves less dangerous, or whether some other feature of the interaction between those parasites and sickle cell hemoglobin accounts for the lower disease rates. The study establishes an association between the sickle cell variant and a particular parasite genotype; it does not establish the mechanism by which that association translates into protection.
Nsango framed the finding in evolutionary terms. "The sickle cell mutation is one of the clearest examples of how infectious diseases can shape human evolution, but our findings suggest that humans also shape the evolution of the parasite in return," she said, as quoted by Genetic Engineering and Biotechnology News. "Understanding these interactions may help us anticipate how malaria parasites adapt in the future and design more effective strategies for malaria control."
The open question is whether the Pfsa-positive variants that appear to thrive in sickle cell carriers are spreading in populations where the trait is common, and whether that has any implications for vaccine or drug design. Answering that would require tracking parasite genotypes across time and geography, not just in a single cross-sectional study of one region. This study is a starting point for that work, not a conclusion.
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