Study Reveals How Malaria Parasite Avoids Immune Detection

Researchers at Weill Cornell Medicine have uncovered how the malaria-causing parasite, Plasmodium falciparum, can evade the human immune system, sometimes remaining undetected for years. The study, published in Nature Microbiology, shows that the parasite can deactivate a key group of genes, making itself “immunologically invisible.”

Malaria infects 300–500 million people annually and is responsible for nearly 600,000 deaths worldwide. Francesca Florini, co-leader of the study, explained, “This finding provides another piece of the puzzle as to why malaria has been so difficult to eradicate.” In malaria-endemic regions, asymptomatic adults may carry hidden parasites that mosquitoes can pick up and transmit to others.

Kirk Deitsch, senior author of the study, noted, “Current campaigns to control malaria focus on treating people, usually children, who show symptoms. These findings suggest that we need to consider asymptomatic adults who can carry potentially transmissible parasites, which means eliminating malaria from any geographical region is going to be more complicated than anticipated.”

Inside the human body, the parasite invades red blood cells and must avoid detection by the immune system and removal by the spleen. It uses about 60 “var” genes, each encoding a protein that can appear on the red blood cell’s surface. By switching which var gene is active, the parasite helps infected cells stick to blood vessel walls and evade the spleen. The immune system eventually recognizes these proteins, so the parasite shifts to another var gene to stay hidden.

Using single-cell sequencing, Florini and co-leader Joseph Visone found that while most parasites activate just one var gene, some activate two or three, and others express none. This “null state” allows the parasite to escape immune detection. Dr. Deitsch suspects these parasites may hide in the bone marrow or in non-circulating red cells within the spleen. He plans further research in West Africa to locate these reservoirs and better understand chronic malaria infections.