Malaria affected an estimated 228 million people worldwide in 2018. However, questions remain unanswered as to how the mosquito-borne malaria parasite Plasmodium infects humans – and how genes against resistance to anti-malarial drugs spread. Different strains of the parasite can exchange genes with each other if they reproduce sexually within a single mosquito, and the resulting mixed strains infect humans through the mosquito bite. A new study paints a detailed picture of how Plasmodium deals with genes, finding that all of the genetic diversity within an actively infected human host – up to 17 strains of the parasite – can come from just one bite. The work was published in Cell Host and Microbe in January.
Plasmodium spends part of its life cycle in humans and part in mosquitoes. In the mosquito it reproduces, mixes and adjusts genes. So far, the most efficient way to study the genetic diversity of Plasmodium has been to grind whole mosquitoes and sequence the mixture. With the new technology, scientists can determine whether a patient’s particular parasites were the product of reproduction within a single mosquito or were introduced separately by different mosquitoes.
The researchers collected blood from patients at a hospital that serves various villages in Malawi, and then sequenced the genomes of the parasites found in infected blood cells. Based on the parasite’s commingled genomes, the researchers found that almost all of the infections studied likely came from a single bite.
“By single-cell sequencing of parasites from entire populations of infected people, we were able to truly see people become infected with malaria for the first time,” said Ian Cheeseman, parasitologist at the Texas Biomedical Research Institute and senior author of the new study. “Sometimes a single mosquito bite can transmit absolutely amazing amounts of genetic diversity.”
The results are consistent with what Dyann Wirth, an infectious disease researcher at Harvard University who specializes in parasites and who was not involved in the new study, suspected based on previous research. She calls the work “an important technical breakthrough that enables a much deeper understanding of the transmission and recombination of malaria”.
This technique can also reveal where infections are coming from. If eradication efforts reduce malaria cases in a given area, analyzing the blood cells of people who are still sick can reveal whether the infected mosquitoes came from afar or whether the local elimination was incomplete, explains Edward Wenger, director of global health research at the Institute for Disease Modeling in Bellevue, Washington, which was not involved in the study. The method could also help researchers track drug resistance mutation proliferation. Finding these mutations – and containing their spread – is an important public health strategy to keep medicines working.