People who carry one copy of the sickle cell variant are infected almost exclusively by a distinct variety of malaria parasite, according to a study published on Oct. 8 in the journal Nature Microbiology.
Researchers from Cameroon and the United States analyzed the genes of more than 2,000 people in Mfou, a rural town in Cameroon, along with the genes of the parasites infecting them. Carriers of the variant were just as likely as everyone else to be infected, but with a different variety of the parasite. And they were a tenth as likely to develop harmful disease, University of Utah Health said in an announcement of the findings.
“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,” said Dr. Sandrine Nsango, an associate professor of molecular biology at the University of Douala in Cameroon and the study’s senior author.
Two copies of the variant cause sickle cell disease. One copy offers protection against malaria, and in places where malaria is most common, the variant turns up at higher rates, a sign of how the disease has pushed human evolution over thousands of years. Why a single copy protects people has been an open question.
Earlier work from the lab where Dr. Ellen Leffler did her postdoctoral research found the unusual parasite strain by studying the rare carriers who did get sick. Scientists first guessed it might be a “superbug,” unusually good at causing disease. The new results point the other way. The researchers wrote that the biology of this parasite variety may account, at least in part, for the protection the trait gives.
The new study looked at infections that cause no symptoms. They were extremely common in Mfou, found in three-quarters of the healthy people studied. Carriers were more likely to harbor one variety of the parasite, while parasites with a different genetic makeup were more common in people without the variant. The researchers said that suggests the variant influences which parasites can infect a person whether or not that person ever falls ill.
Dr. Leffler, an assistant professor of human genetics at University of Utah Health and another senior author, said the pattern had been easy to miss.
“It’s still kind of surprising that was under the radar. It was hiding in plain sight. People have been looking at this association for a long time, but you have to be able to ask the parasite for it to tell you this.”
She said the work offered “a new dimension to try to understand what determines the outcomes of infection,” and that she hoped it would lead “ideally to some practical new strategies for tracking or treating infections.”
The paper, titled “Sickle cell haemoglobin status shapes malaria parasite genotype in asymptomatic infections,” was supported by the Fondation Pierre Fabre, through its IMPAS project, and by the American Heart Association.
“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,” Dr. Nsango said. “Understanding these interactions may help us anticipate how malaria parasites adapt in the future and design more effective strategies for malaria control.”